Research Topics
Genomes and Genes | Michael A BrehmSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
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Publications
Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCFMichael A Brehm
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Blood 119:2778-88. 2012..These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development...
Human allograft rejection in humanized mice: a historical perspectiveMichael A Brehm
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Cell Mol Immunol 9:225-31. 2012..Here, we present a historical perspective on the study of allograft rejection in humanized mice and discuss the use of these novel model systems in transplant biology...- Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in miceMichael 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... - Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutationMichael A Brehm
Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Clin Immunol 135:84-98. 2010..Our data define key parameters for establishing humanized mouse models to study human immunity... - Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita miceMichael A Brehm
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Diabetes 59:2265-70. 2010..To create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system... - TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockadeDavid 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... 
Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infectionsMichael 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...- CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infectionsMarkus 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... - Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD miceJulie Mangada
Program in Immunology and Virology, The University of Massachusetts Medical School, Worcester, Massachusetts, USA
Diabetes 58:165-73. 2009..However, costimulation blockade-based tolerance protocols have failed in prolonging islet allograft survival in NOD mice... - TLR agonists abrogate costimulation blockade-induced prolongation of skin allograftsThomas 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... - Rapid conversion of effector mechanisms from NK to T cells during virus-induced lysis of allogeneic implants in vivoMichael 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... - Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory development and is an intrinsic property of the epitopeXiaoting 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... - TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation toleranceDavid M Miller
Department of Medicine, Division of Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Ann N Y Acad Sci 1150:149-51. 2008.... - Type 1 IFN mediates cross-talk between innate and adaptive immunity that abrogates transplantation toleranceThomas 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... - Narrowed TCR repertoire and viral escape as a consequence of heterologous immunityMarkus 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... - Protection against vaccinia virus challenge by CD8 memory T cells resolved by molecular mimicryMarkus Cornberg
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
J Virol 81:934-44. 2007.... - Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host diseaseSteve Pino
Department of Medicine, The University of Massachusetts Medical School, Worcester, MA, USA
Methods Mol Biol 602:105-17. 2010.... - Bi-specific MHC heterodimers for characterization of cross-reactive T cellsZu 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... - Heterologous immunity between virusesRaymond 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... - Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunityLiisa K Selin
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Immunol Rev 211:164-81. 2006.... - Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell helpLuana 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... - Rapid production of TNF-alpha following TCR engagement of naive CD8 T cellsMichael A Brehm
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 175:5043-9. 2005.... - CD8 memory T cells: cross-reactivity and heterologous immunityLiisa 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... - CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cellsSteven C Pino
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
PLoS ONE 4:e5468. 2009..These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells... - Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulationSung 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... - Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominanceIan A York
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Proc Natl Acad Sci U S A 103:9202-7. 2006..Moreover, peptide trimming and the resulting abundance of peptide-MHC complexes are dominant factors in establishing immunodominance... - Virus-specific CD8 T cells in peripheral tissues are more resistant to apoptosis than those in lymphoid organsXiaoting 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... - CD8 T cell responses to viral infections in sequenceMichael 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... - Maturation-dependent licensing of naive T cells for rapid TNF productionBhavana 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... - Heterologous immunity and the CD8 T cell networkLiisa K Selin
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Springer Semin Immunopathol 24:149-68. 2002 - Frontiers in nephrology: heterologous immunity, T cell cross-reactivity, and alloreactivityLiisa K Selin
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
J Am Soc Nephrol 18:2268-77. 2007.... - Humanized mice for the study of type 1 and type 2 diabetesDale L Greiner
University of Massachusetts Medical School, Worcester, Massachusetts, USA
Ann N Y Acad Sci 1245:55-8. 2011..The availability of immunodeficient mice engrafted with functional human immune systems and islets permits in vivo study of human diabetes without putting patients at risk... - T-cell activation and transplantation toleranceBhavana Priyadharshini
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Transplant Rev (Orlando) 26:212-22. 2012.... - Humanized mouse models to study human diseasesMichael A Brehm
Diabetes Division, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Curr Opin Endocrinol Diabetes Obes 17:120-5. 2010..Update on humanized mouse models and their use in biomedical research... - Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunityMelissa Woelfel
Department of Pathology, Immunology and Virology Program, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 177:3814-20. 2006..Thus, the MC159-Tg mice provide a model to study the effects of PCD in immune responses without hampering other important lymphocyte functions... - Dynamic glucoregulation and mammalian-like responses to metabolic and developmental disruption in zebrafishAgata Jurczyk
University of Massachusetts Medical School, Diabetes Center of Excellence, 373 Plantation Street, Suite 218, Worcester, MA 01605, USA
Gen Comp Endocrinol 170:334-45. 2011..In summary, we identify mechanisms of glucoregulation in zebrafish embryos that are conserved with embryonic and adult mammals. These observations justify use of this model in mechanistic studies of human metabolic disease... - Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG miceSmita Jaiswal
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
Immunology 136:334-43. 2012..The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections... - Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient miceMichael A Brehm
University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts, USA
Cold Spring Harb Perspect Med 2:a007757. 2012..With this, these so-called "humanized mice" are currently being used as a preclinical bridge to facilitate identification and translation of novel discoveries to clinical settings... - T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogensMichael 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... - Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppressionDavid V Serreze
The Jackson Laboratory, Bar Harbor, ME 04609, USA
J Immunol 177:6675-84. 2006....