Raymond M Welsh

Summary

Affiliation: University of Massachusetts Medical School
Country: USA

Publications

  1. pmc NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections
    Raymond M Welsh
    Department of Pathology and Program for Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Virology 435:37-45. 2013
  2. pmc Murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to Ly49H
    K A Daniels
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Exp Med 194:29-44. 2001
  3. pmc Blimp hovers over T cell immunity
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunity 31:178-80. 2009
  4. pmc Heterologous immunity between viruses
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Rev 235:244-66. 2010
  5. ncbi request reprint Private specificities of heterologous immunity
    Raymond M Welsh
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Opin Immunol 18:331-7. 2006
  6. ncbi request reprint Immunological memory to viral infections
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Annu Rev Immunol 22:711-43. 2004
  7. ncbi request reprint The privacy of T cell memory to viruses
    R M Welsh
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Top Microbiol Immunol 311:117-53. 2006
  8. ncbi request reprint Pathogenic epitopes, heterologous immunity and vaccine design
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Nat Rev Microbiol 5:555-63. 2007
  9. ncbi request reprint Apoptosis and loss of virus-specific CD8+ T-cell memory
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Opin Immunol 16:271-6. 2004
  10. pmc Attrition of memory CD8 T cells
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 459:E3-4; discussion E4. 2009

Research Grants

  1. B cell activation during viral infection
    Raymond M Welsh; Fiscal Year: 2010
  2. REGULATION OF NATURAL KILLER CELLS
    Raymond Welsh; Fiscal Year: 1993
  3. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond Welsh; Fiscal Year: 2003
  4. IMMUNITY AND VIRUS DISEASE
    Raymond Welsh; Fiscal Year: 2003
  5. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond M Welsh; Fiscal Year: 2010
  6. B cell activation during viral infection
    Raymond Welsh; Fiscal Year: 2007
  7. IMMUNITY AND VIRUS DISEASE
    Raymond Welsh; Fiscal Year: 2007
  8. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond Welsh; Fiscal Year: 2007
  9. TRAINING IN IMMUNOLOGY
    Raymond Welsh; Fiscal Year: 2006
  10. REGULATION OF NATURAL KILLER CELLS
    Raymond Welsh; Fiscal Year: 2005

Collaborators

Detail Information

Publications93

  1. pmc NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections
    Raymond M Welsh
    Department of Pathology and Program for Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Virology 435:37-45. 2013
    ..This subsequent change in T cell dynamics can alter patterns of immunopathology and persistence and implicates NK cells as rheostat-like regulators of persistent infections...
  2. pmc Murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to Ly49H
    K A Daniels
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Exp Med 194:29-44. 2001
    ..1(+)CD3(-) NK cells and not to NK1.1(+)CD3(+) "NK/T" cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset...
  3. pmc Blimp hovers over T cell immunity
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunity 31:178-80. 2009
    ..2009; Rutishauser et al., 2009; Shin et al., 2009) indicate that the transcriptional repressor Blimp-1 promotes the development of short-lived effector cells and regulates clonal exhaustion...
  4. pmc Heterologous immunity between viruses
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Rev 235:244-66. 2010
    ..We propose that heterologous immunity is an important factor in resistance to and variations of human viral infections and that issues of heterologous immunity should be considered in the design of vaccines...
  5. ncbi request reprint Private specificities of heterologous immunity
    Raymond M Welsh
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Opin Immunol 18:331-7. 2006
    ..The significance of the private specificities of these repertoires is brought about under conditions of heterologous immunity and might have important consequences in anti-viral immunity and immunopathology...
  6. ncbi request reprint Immunological memory to viral infections
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Annu Rev Immunol 22:711-43. 2004
    ..Here we describe how T and B cell memory is generated in response to virus infections and how these cells respond when the host is infected again by similar or different viruses...
  7. ncbi request reprint The privacy of T cell memory to viruses
    R M Welsh
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Top Microbiol Immunol 311:117-53. 2006
    ..Examples are given of how the private specificities of immune responses under conditions of heterologous immunity influence the pathogenesis of murine and human viral infections...
  8. ncbi request reprint Pathogenic epitopes, heterologous immunity and vaccine design
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Nat Rev Microbiol 5:555-63. 2007
    ..We suggest that the specific removal of such pathogenic epitopes from vaccines might increase their prophylactic potential, while minimizing the risk of side-effects from vaccine use...
  9. ncbi request reprint Apoptosis and loss of virus-specific CD8+ T-cell memory
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Opin Immunol 16:271-6. 2004
    ..Persistent infections can induce apoptotic deletions of memory T cells that are specific to the persisting virus and to previously encountered pathogens...
  10. pmc Attrition of memory CD8 T cells
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 459:E3-4; discussion E4. 2009
    ..We show here in Fig. 1 that a series of infections can indeed reduce the total number of memory cells, indicating that vaccination strategies need to consider this issue...
  11. pmc TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade
    David M Miller
    Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 182:5547-59. 2009
    ..These data suggest that distinct but overlapping cellular and molecular mechanisms control the ability of TLR agonists to block tolerance induction to hematopoietic and skin allografts in mice treated with costimulation blockade...
  12. ncbi request reprint Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 170:4077-86. 2003
    ..Mice previously infected with LCMV and harboring allo-specific memory T cells were refractory to the induction of tolerance to allogeneic skin grafts...
  13. ncbi request reprint IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections
    Kapil Bahl
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Immunol 176:4284-95. 2006
    ..In addition, computer models indicated that early depletion of memory T cells may allow for the generation for a more diverse T cell response to infection by reducing the immunodomination caused by cross-reactive T cells...
  14. pmc CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections
    Markus Cornberg
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 184:2825-38. 2010
    ..Defining such cross-reactive networks between commonly encountered human pathogens may facilitate the design of vaccines...
  15. ncbi request reprint Rapid conversion of effector mechanisms from NK to T cells during virus-induced lysis of allogeneic implants in vivo
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Immunol 174:6663-71. 2005
    ..This rapid generation of allospecific CTL activity during a viral infection preceded the peak of viral epitope-specific T cell responses, as detected by in vivo or in vitro cytotoxicity assays...
  16. pmc Generation of protective T cell-independent antiviral antibody responses in SCID mice reconstituted with follicular or marginal zone B cells
    Heath M Guay
    Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Immunol 183:518-23. 2009
    ..These findings demonstrate the plasticity of the B cell subsets in virus-infected hosts and show for the first time that B cells derived exclusively from Fo B cells can effectively function in antiviral TI-2 responses...
  17. ncbi request reprint Cutting edge: MHC class II-restricted killing in vivo during viral infection
    Evan R Jellison
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 174:614-8. 2005
    ..In this study, we demonstrate CD4-dependent MHC class II-restricted killing in lymphocytic choriomeningitis virus-infected mice in vivo using an in vivo cytotoxicity assay that features class II-expressing B cells as targets...
  18. ncbi request reprint Attrition of virus-specific memory CD8+ T cells during reconstitution of lymphopenic environments
    Craig D Peacock
    Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    J Immunol 171:655-63. 2003
    ....
  19. ncbi request reprint Type 1 IFN mediates cross-talk between innate and adaptive immunity that abrogates transplantation tolerance
    Thomas B Thornley
    Department of Medicine, Division of Diabetes, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 179:6620-9. 2007
    ..Blocking of type 1 IFN-dependent pathways in patients may improve allograft survival in the presence of exogenous TLR ligands...
  20. ncbi request reprint TLR agonists abrogate costimulation blockade-induced prolongation of skin allografts
    Thomas B Thornley
    Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 176:1561-70. 2006
    ..We conclude that TLR signaling abrogates the effects of costimulation blockade by preventing alloreactive CD8+ T cell apoptosis through a mechanism not dependent on TNFR2 or IL-12R signaling...
  21. pmc Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Blood 109:819-26. 2007
    ..We conclude that rapid production of TNF-alpha can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection...
  22. ncbi request reprint Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections
    Sung Kwon Kim
    Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    J Immunol 172:3139-50. 2004
    ..This study therefore links an early virus-induced lymphopenia to a subsequent long-term loss of CD8 T cell memory and offers a new mechanism for immune deficiency during persistent viral infections...
  23. pmc Private specificities of CD8 T cell responses control patterns of heterologous immunity
    Sung Kwon Kim
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Exp Med 201:523-33. 2005
    ..This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases...
  24. ncbi request reprint Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory development and is an intrinsic property of the epitope
    Xiaoting Z Wang
    Program in Immunology and Virology, Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    J Immunol 173:5138-47. 2004
    ..The tissue-dependent and epitope-dependent preapoptotic state correlated with reduced expression of IL-7Ralpha...
  25. pmc Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity
    Markus Cornberg
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School UMMS, Worcester, Massachusetts 01655, USA
    J Clin Invest 116:1443-56. 2006
    ..This has implications for the design of peptide-based vaccines, which might unintentionally prime for skewed TCR responses to cross-reactive epitopes...
  26. pmc Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes
    Shalyn C Clute
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 185:6753-64. 2010
    ..We suggest that dissimilar cross-reactive epitopes might generate a broad, rather than a narrow, T cell repertoire if there is a lack of dominant high-affinity clones; this hypothesis is supported by computer simulation...
  27. pmc IFN-alpha beta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions
    Heather D Marshall
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 185:1419-28. 2010
    ....
  28. pmc NK cells and gammadelta T cells mediate resistance to polyomavirus-induced tumors
    Rabinarayan Mishra
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Pathog 6:e1000924. 2010
    ..Our findings demonstrate a protective role for NK and gammadelta T cells against naturally occurring virus-induced tumors and suggest the involvement of NKG2D-mediated mechanisms...
  29. pmc Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses
    Sue Jane Lin
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Blood 112:680-9. 2008
    ..Thus, whereas an HP immune system is capable of mounting relatively normal acute and memory CD8 T-cell responses, the narrowing of the T-cell repertoire may reduce immune responses to subsequently encountered pathogens...
  30. pmc High frequencies of virus-specific CD8+ T-cell precursors
    Mina O Seedhom
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Virol 83:12907-16. 2009
    ..These results show that frequencies of naïve and memory CD8(+) T cell precursors for whole viruses can be remarkably high...
  31. pmc Pathological features of heterologous immunity are regulated by the private specificities of the immune repertoire
    Siwei Nie
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Am J Pathol 176:2107-12. 2010
    ..This indicates that virus-induced immunopathology under conditions of heterologous immunity is a function of the private specificity of the immune repertoire...
  32. pmc Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-MHC structural features recognized by cross-reactive T cells
    Zu T Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655
    J Immunol 191:5139-52. 2013
    ..These results indicate that protective heterologous immune responses can occur for disparate epitopes from unrelated viruses. ..
  33. ncbi request reprint Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Rev 211:164-81. 2006
    ....
  34. pmc Increased protection from vaccinia virus infection in mice genetically prone to lymphoproliferative disorders
    Mina O Seedhom
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:6010-22. 2012
    ..These results suggest that IFN-γ produced by multiple activated leukocyte populations in Fas-deficient hosts enhances resistance to some viral infections...
  35. ncbi request reprint Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen
    Evan R Jellison
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Eur J Immunol 37:119-28. 2007
    ..This approach, therefore, formally demonstrates and quantifies a virus-induced polyclonal proliferation and differentiation of B cells, which, due to their high proportion, would mostly have BCR not specific for the virus...
  36. pmc Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation
    Sue Jane Lin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Exp Med 204:2321-33. 2007
    ..These results suggest that PD-1 may play a negative regulatory role to control rapidly proliferating and potentially pathogenic autoreactive CD8+ T cells during homeostatic reconstitution of lymphopenic environments...
  37. ncbi request reprint Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help
    Luana O Atherly
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 176:1571-81. 2006
    ..These defects cannot be rescued by providing virus-specific CD4(+) T cell help, thereby substantiating the important role of Tec kinases in CD8(+) T cell signaling...
  38. ncbi request reprint Infections that induce autoimmune diabetes in BBDR rats modulate CD4+CD25+ T cell populations
    Danny Zipris
    Program in Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 170:3592-602. 2003
    ....
  39. pmc Bi-specific MHC heterodimers for characterization of cross-reactive T cells
    Zu T Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 285:33144-53. 2010
    ..A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans...
  40. ncbi request reprint Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation
    Sung Kwon Kim
    Department of Pathology, University of Massachusetts, Worcester, MA 01655, USA
    J Immunol 169:90-8. 2002
    ..Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity...
  41. pmc Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis
    Stephen N Waggoner
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 120:1925-38. 2010
    ..These results illustrate the importance of NK cell self-tolerance to activated CD8+ T cells and demonstrate how an apparent T cell-associated persistent infection can actually be regulated by NK cells...
  42. ncbi request reprint T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens
    Michael A Brehm
    Department of Pathology and Progranm in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Nat Immunol 3:627-34. 2002
    ..Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology...
  43. pmc Immunogenicity of influenza virus vaccine is increased by anti-gal-mediated targeting to antigen-presenting cells
    Ussama M Abdel-Motal
    Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, LRB, Worcester, MA 01605, USA
    J Virol 81:9131-41. 2007
    ..We suggest that a similar method for increasing immunogenicity may be applicable to avian influenza vaccines...
  44. pmc Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis
    Shalyn C Clute
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 115:3602-12. 2005
    ..Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM...
  45. pmc Natural killer cells act as rheostats modulating antiviral T cells
    Stephen N Waggoner
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Nature 481:394-8. 2012
    ..Thus, NK cells can act as rheostats, regulating CD4 T-cell-mediated support for the antiviral CD8 T cells that control viral pathogenesis and persistence...
  46. ncbi request reprint Virus-specific CD8 T cells in peripheral tissues are more resistant to apoptosis than those in lymphoid organs
    Xiaoting Z Wang
    Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    Immunity 18:631-42. 2003
    ..This may contribute to the survival of nondividing peripheral memory T cells, enabling them to efficiently function without being driven into apoptosis...
  47. pmc Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus
    Yuri N Naumov
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 181:7407-19. 2008
    ....
  48. pmc T-Cell-independent immunoglobulin G responses in vivo are elicited by live-virus infection but not by immunization with viral proteins or virus-like particles
    E Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA
    J Virol 72:6665-70. 1998
    ..Germinal centers were not observed in T-cell-deficient PyV-infected mice, indicating that the germinal center pathway of B-cell differentiation is TD even in the context of a virus infection...
  49. pmc Inflammatory cytokine-mediated evasion of virus-induced tumors from NK cell control
    Rabinarayan Mishra
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 191:961-70. 2013
    ..Thus, our data suggest a new mechanism whereby inflammatory cytokines generated in the tumor environment lead to evasion of NK cell-mediated control of virus-induced tumors. ..
  50. ncbi request reprint CD8 memory T cells: cross-reactivity and heterologous immunity
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Semin Immunol 16:335-47. 2004
    ..Here we discuss examples of altered viral pathogenesis occurring as a consequence of heterologous T cell immunity and propose models for the maintenance of a dynamic pool of memory cells...
  51. pmc Role for TLR2 in NK cell-mediated control of murine cytomegalovirus in vivo
    Eva Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, Massachusetts 01655, USA
    J Virol 80:4286-91. 2006
    ..Our studies suggest that in addition to the reported involvement of TLR9 and TLR3, TLR2 is also involved in innate immune responses to MCMV infection...
  52. pmc Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope
    Alex T Chen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Pathog 8:e1002633. 2012
    ..Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses...
  53. pmc CD4 T-cell-mediated heterologous immunity between mycobacteria and poxviruses
    Keisha S Mathurin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Virol 83:3528-39. 2009
    ..This study therefore demonstrates CD4 T-cell-mediated heterologous immunity between a bacterium and virus. Further, it poses the question of whether BCG immunization of humans alters resistance to unrelated pathogens...
  54. ncbi request reprint CD8 T cell responses to viral infections in sequence
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell Microbiol 6:411-21. 2004
    ..Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence...
  55. ncbi request reprint MyD88 is required for the formation of long-term humoral immunity to virus infection
    Heath M Guay
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 178:5124-31. 2007
    ..Our findings show that MyD88-dependent signaling pathways in B cells are essential for effectively generating long-term Ab responses and implicate a role for TLR in the formation of long-term humoral immunity...
  56. ncbi request reprint Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 175:5043-9. 2005
    ....
  57. ncbi request reprint Plasticity of T cell memory responses to viruses
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Immunity 20:5-16. 2004
    ..This is in part accounted for by crossreactive memory T cells, which can be employed in immune responses and mediate protective immunity or life-threatening immunopathology...
  58. pmc Mice completely lacking immunoproteasomes show major changes in antigen presentation
    Eleanor Z Kincaid
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Nat Immunol 13:129-35. 2012
    ..These results indicated that immunoproteasomes were more important in antigen presentation than previously thought...
  59. pmc Maturation-dependent licensing of naive T cells for rapid TNF production
    Bhavana Priyadharshini
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS ONE 5:e15038. 2010
    ..Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs...
  60. ncbi request reprint Origin and fate of lymphocytic choriomeningitis virus-specific CD8+ T cells coexpressing the inhibitory NK cell receptor Ly49G2
    Craig D Peacock
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Immunol 173:478-84. 2004
    ..We suggest that G2+CD8+ cells represent a cell lineage distinct from bona fide memory T cells, but that they can participate in an acute virus-specific T cell response...
  61. pmc Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung
    Hong D Chen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Am J Pathol 163:1341-55. 2003
    ..Heterologous immunity thus occurs between many viruses, resulting in altered protective immunity and lung immunopathology, and this is influenced by the specific virus infection sequence...
  62. pmc Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon
    Heather D Marshall
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Virol 85:5929-39. 2011
    ..Inhibition of T cell receptor-stimulated bystander CD8 T cell proliferation during acute viral infections may reflect the reduced ability of vaccines to elicit protective immunity when administered during an acute illness...
  63. pmc Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists
    Kapil Bahl
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 84:4866-77. 2010
    ..Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells...
  64. ncbi request reprint No one is naive: the significance of heterologous T-cell immunity
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    Nat Rev Immunol 2:417-26. 2002
    ..Here, we discuss evidence from studies in mice and humans that shows the importance of this phenomenon in determining the outcome of infection...
  65. ncbi request reprint Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells
    L K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Immunol 166:6784-94. 2001
    ..Thus, gammadelta T cells can be mediators of innate immunity to viruses, having a significant impact on virus replication early in infection in the presence or absence of the adaptive immune response...
  66. pmc Epigenetic modifications induced by Blimp-1 Regulate CD8⁺ T cell memory progression during acute virus infection
    Hyun Mu Shin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunity 39:661-75. 2013
    ..These data elucidate a central mechanism by which Blimp-1 acts as an epigenetic regulator and enhances the numbers of short-lived effector cells while suppressing the development of memory-precursor CD8⁺ T cells...
  67. pmc Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses
    J M McNally
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Ave. N, Worcester, MA 01655, USA
    J Virol 75:5965-76. 2001
    ..Apoptotic attrition of bystander T cells may make room for the antigen-specific expansion of T cells during infection and may, in part, account for the loss of T-cell memory that occurs when the host undergoes subsequent infections...
  68. pmc Lymphocytic choriomeningitis virus (LCMV): propagation, quantitation, and storage
    Raymond M Welsh
    University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Curr Protoc Microbiol . 2008
    ..Recommendations are made for techniques for propagating LCMV to high titers to quantify it by plaque assay and PCR techniques and to preserve its infectivity by appropriate storage...
  69. pmc Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations
    L K Selin
    Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA
    J Exp Med 188:1705-15. 1998
    ..These results indicate that how a host responds to an infectious agent is a function of its history of previous infections and their influence on the memory T cell pool...
  70. ncbi request reprint Antiviral T-cell-independent type 2 antibody responses induced in vivo in the absence of T and NK cells
    E Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA
    Virology 280:160-8. 2001
    ....
  71. ncbi request reprint Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses
    L K Selin
    Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    Immunity 11:733-42. 1999
    ..These results are consistent with a model for the immune system that accommodates memory T cell populations for multiple pathogens over the course of a lifetime...
  72. ncbi request reprint The role of CD40-CD154 interaction in antiviral T cell-independent IgG responses
    E Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 164:5877-82. 2000
    ..Our studies demonstrate that, although about half of the TI IgG responses to PyV are independent of CD40-CD40L interactions, these interactions occur in T cell-deficient mice and enhance antiviral TI Ab responses...
  73. ncbi request reprint Dynamics of Ly49 expressing cytotoxic lymphocyte subsets in response to virus infection
    Craig D Peacock
    Department of Pathology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA
    Microbes Infect 4:1481-90. 2002
    ..CD8(+) T cells expressing Ly49G2 were selectively expanded by poly I:C and participated in the antigen-specific response to lymphocytic choriomeningitis virus...
  74. pmc Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells
    C H Tay
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    J Virol 71:267-75. 1997
    ..These results may explain why the Cmv-lr locus, which maps closely to genes regulating NK cell cytotoxic function, confers an NK cell-dependent resistance to MCMV infection in the spleen but not in the liver...
  75. pmc Judging a virus by its cover
    Eva Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 114:895-7. 2004
    ....
  76. pmc Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections
    L K Selin
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    J Exp Med 183:2489-99. 1996
    ..This demonstrates that virus infections do not occur in immunological isolation, and that CD8+ T cell responses are continually being modulated by other infectious agents...
  77. ncbi request reprint Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: relative stability of CD4 memory under conditions of CD8 memory T cell loss
    S M Varga
    Program in Immunology and Virology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    J Immunol 166:1554-61. 2001
    ....
  78. ncbi request reprint T-cell-independent antiviral antibody responses
    E Szomolanyi-Tsuda
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    Curr Opin Immunol 10:431-5. 1998
    ..Inactivated virus or virus-like particles can stimulate IgM production, but factors induced during live virus infection appear to be required to induce the isotype switch that leads to IgG or IgA responses...
  79. ncbi request reprint Viral abrogation of stem cell transplantation tolerance causes graft rejection and host death by different mechanisms
    Daron Forman
    Program in Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 168:6047-56. 2002
    ..Clinical application of stem cell transplantation protocols based on costimulation blockade and tolerance induction may require patient isolation to facilitate the procedure and to protect recipients...
  80. ncbi request reprint Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung
    H D Chen
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Nat Immunol 2:1067-76. 2001
    ..Thus, the participation of pre-existing memory T cells specific to unrelated agents can alter the dynamics of mucosal immunity and disease course in response to a pathogen...
  81. pmc Virus-induced abrogation of transplantation tolerance induced by donor-specific transfusion and anti-CD154 antibody
    R M Welsh
    Departments of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Virol 74:2210-8. 2000
    ..Clinical application of transplantation tolerance protocols may require patient isolation to facilitate the procedure and to protect recipients...
  82. ncbi request reprint Alpha beta and gamma delta T-cell networks and their roles in natural resistance to viral infections
    R M Welsh
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    Immunol Rev 159:79-93. 1997
    ..Thus, memory alpha beta T cells can, like gamma delta T cells and NK cells, provide natural immunity to viral infections...
  83. pmc Apoptotic regulation of T cells and absence of immune deficiency in virus-infected gamma interferon receptor knockout mice
    B L Lohman
    Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA
    J Virol 72:7815-21. 1998
    ..This finding indicates that clonal exhaustion of CTL does not require IFN-gamma or Fas, even though both molecules influence AICD and the transient immune deficiency seen in the LCMV infection...
  84. ncbi request reprint Immune deficiency, immune silencing, and clonal exhaustion of T cell responses during viral infections
    R M Welsh
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Curr Opin Microbiol 2:382-7. 1999
    ..These new techniques have shown that functional inactivation and apoptotic elimination of both virus-specific and non-virus-specific T cell populations mold T cell responses to viral infections...
  85. pmc Mycoplasma infection induces a scleroderma-like centrosome autoantibody response in mice
    I Gavanescu
    Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Clin Exp Immunol 137:288-97. 2004
    ..Antibiotic treatment of mice prevents autoantibody development. Centrosome autoantibodies may provide an aetiological link between infection and human autoimmunity and suggest novel therapeutic strategies in these disorders...
  86. ncbi request reprint Bystander T cell activation and attrition
    J M McNally
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical Center, Worcester, MA 01655, USA
    Curr Top Microbiol Immunol 263:29-41. 2002
  87. pmc Evaluation of the Galalpha1-3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses
    R M Welsh
    Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA
    J Virol 72:4650-6. 1998
    ....
  88. pmc Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity
    M A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA
    Am J Transplant 10:1738-48. 2010
    ..Last, we show that purified LCMV-specific CD8 T cells rejected skin allografts in SCID mice. These findings therefore implicate a potential role for heterologous immunity in virus-induced allograft rejection...
  89. ncbi request reprint B cell memory: sapping the T cell
    Raymond M Welsh
    Nat Med 9:164-6. 2003
  90. ncbi request reprint Tumor viral escape from inhibited T cells
    Raymond M Welsh
    Nat Immunol 3:112-4. 2002
  91. ncbi request reprint Dengue immune response: low affinity, high febrility
    Raymond M Welsh
    Nat Med 9:820-2. 2003
  92. pmc Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction
    Hailin Yang
    Laboratory of Immunobiology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Clin Invest 115:379-87. 2005
    ..Collectively, these findings show that chemical inhibitors of host-signaling pathways exploited by viral pathogens may represent potent antiviral therapies...
  93. ncbi request reprint Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies
    Mikyung Kim
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:25838-48. 2004
    ..These findings suggest that blockade of pathogenic factor actions, in general, may be advantageous to the infected host...

Research Grants64

  1. B cell activation during viral infection
    Raymond M Welsh; Fiscal Year: 2010
    ..Understanding how humoral immunity is maintained will shed light on strategies for the development of long term protective vaccination-induced antibody responses. ..
  2. REGULATION OF NATURAL KILLER CELLS
    Raymond Welsh; Fiscal Year: 1993
    ..The proposed experiments should help elucidate how NK cells respond to stimuli within an infected animal, such that they may effectively contribute to natural immunity...
  3. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond Welsh; Fiscal Year: 2003
    ..abstract_text> ..
  4. IMMUNITY AND VIRUS DISEASE
    Raymond Welsh; Fiscal Year: 2003
    ..By manipulating this highly defined LCMV model in vivo, fundamental concepts concerning immunoregulation and immune deficiencies applicable to human viral infections should be obtained. ..
  5. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond M Welsh; Fiscal Year: 2010
    ..Understanding the implications of this "heterologous immunity" in normal and aged hosts should enhance our knowledge of viral pathogenesis and contribute to the design of better vaccines. ..
  6. B cell activation during viral infection
    Raymond Welsh; Fiscal Year: 2007
    ..Understanding how humoral immunity is maintained will shed light on strategies for the development of long term protective vaccination-induced antibody responses. ..
  7. IMMUNITY AND VIRUS DISEASE
    Raymond Welsh; Fiscal Year: 2007
    ..abstract_text> ..
  8. VIRUS INDUCED IMMUNOPATHOLOGY
    Raymond Welsh; Fiscal Year: 2007
    ..SPECIFIC AIM #4. To determine the basis for the deficiency of virus-specific T cells in the homeostatic reconstitution of lymphopenic environments. ..
  9. TRAINING IN IMMUNOLOGY
    Raymond Welsh; Fiscal Year: 2006
    ..This Immunology Training Grant has been an integral part of our program for the past 12 years, and we are requesting another 5 years of support. ..
  10. REGULATION OF NATURAL KILLER CELLS
    Raymond Welsh; Fiscal Year: 2005
    ..This work should clarify how these effector systems act and interact to rid the host of infectious agents and tumors. ..
  11. REGULATION OF NATURAL KILLER CELLS
    Raymond Welsh; Fiscal Year: 1999
    ..to do a molecular analysis of NK- sensitive and NK-resistant variants of PV, in order to determine which viral gene product confers the phenotype of NK-sensitivity. ..
  12. IMMUNITY AND VIRUS DISEASE
    Raymond Welsh; Fiscal Year: 1993
    ..This work should help define the parameters of natural immunity to virus infections and will determine whether natural effector cells can be used to control infections therapeutically...