Research Topics
Genomes and Genes
| E John WherrySummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
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Detail Information
Publications
T cell exhaustionE John Wherry
Department of Microbiology, Institute for Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Nat Immunol 12:492-9. 2011....
Technical Advance: Fluorescent reporter reveals insights into eomesodermin biology in cytotoxic lymphocytesMichael A Paley
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Leukoc Biol 93:307-15. 2013..Thus, the murine Eomes(gfp)-targeted allele provides a novel opportunity to explore Eomes biology in cytotoxic lymphocytes...- A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infectionHaina Shin
Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA 19104, USA
Immunity 31:309-20. 2009..Thus, we identify Blimp-1 as a transcriptional regulator of CD8(+) T cell exhaustion during chronic viral infection and propose that Blimp-1 acts as a transcriptional rheostat balancing effector function and T cell exhaustion... - Cutting edge: The transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell nicheArnob Banerjee
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 185:4988-92. 2010.... - Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockadeNobuhiro Nakamoto
Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA
PLoS Pathog 5:e1000313. 2009.... - Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesoderminAndrew M Intlekofer
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 321:408-11. 2008..T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction... - Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infectionShawn D Blackburn
Immunology Program and Wistar Vaccine Center, Wistar Institute, Philadelphia, Pennsylvania 19104, USA
Nat Immunol 10:29-37. 2009..Thus, CD8+ T cell responses during chronic viral infections are regulated by complex patterns of coexpressed inhibitory receptors... 
Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memoryTravis A Doering
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Immunity 37:1130-44. 2012..These data identify pathways involved in CD8(+) T cell exhaustion, and highlight the context-dependent nature of transcription factors in exhaustion versus memory...- Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cellsKarla R Wiehagen
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Blood 116:5560-70. 2010..Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence... - Cell-intrinsic defects in the proliferative response of antiviral memory CD8 T cells in aged mice upon secondary infectionVilma Decman
Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA
J Immunol 184:5151-9. 2010..Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity... - Antiviral memory CD8 T-cell differentiation, maintenance, and secondary expansion occur independently of MyD88Adeeb H Rahman
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Blood 117:3123-30. 2011..Our findings clarify the importance of MyD88 during distinct phases of the antiviral T-cell response and establish differential dependence on MyD88 signaling as a novel characteristic that distinguishes naive from memory CD8 T cells... - Commensal bacteria calibrate the activation threshold of innate antiviral immunityMichael C Abt
Department of Microbiology and Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA
Immunity 37:158-70. 2012..Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity... - Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infectionCharlly Kao
Department of Microbiology and Institute for Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Nat Immunol 12:663-71. 2011..Persistent antigenic stimulation caused downregulation of T-bet, which resulted in more severe exhaustion of CD8(+) T cells. Our observations suggest therapeutic opportunities involving higher T-bet expression during chronic infection... - Dynamic T cell migration program provides resident memory within intestinal epitheliumDavid Masopust
Department of Microbiology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
J Exp Med 207:553-64. 2010..These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation... - MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infectionAdeeb H Rahman
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia PA 19104, USA
J Immunol 181:3804-10. 2008.... - Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infectionJill M Angelosanto
Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
J Virol 86:8161-70. 2012..These studies have implications for our understanding of senescence versus exhaustion and for therapeutic interventions during chronic infection... - Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursorsVilma Decman
Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
J Immunol 188:1933-41. 2012..Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity... - T-cell receptor signals direct the composition and function of the memory CD8+ T-cell poolJennifer E Smith-Garvin
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA
Blood 116:5548-59. 2010..Furthermore, we show that TCR signals sufficient to promote CD8(+) T-cell differentiation are different from those required to elicit inflammatory cytokine production... - Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infectionMichael A Paley
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 338:1220-5. 2012..Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections... - Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissuesKerry A Casey
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA
J Immunol 188:4866-75. 2012.... - Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiationSurojit Sarkar
Department of Microbiology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
J Immunol 179:6704-14. 2007..Thus, long-lasting, Ag-independent CD8 T cell memory results from progressive differentiation of memory CD8 T cells, and the rate of memory T cell differentiation is governed by events occurring early during T cell priming... - Selective expansion of a subset of exhausted CD8 T cells by alphaPD-L1 blockadeShawn D Blackburn
Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 105:15016-21. 2008..These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections... - The contribution of epigenetic memory to immunologic memoryValerie P Zediak
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States
Curr Opin Genet Dev 21:154-9. 2011..This gives strength to the concept of gene poising, and has shown that memory T lymphocytes are an ideal model in which to further define various mechanisms of epigenetic poising... - Plasmacytoid dendritic cells are dispensable during primary influenza virus infectionAmaya I Wolf
Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA
J Immunol 182:871-9. 2009..Taken together, our study suggests that pDC regulate the accumulation of T cells in the bronchoalveolar space during early influenza virus infection, but are dispensable for the control of this disease... - Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cellsGeorge Makedonas
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
PLoS Pathog 6:e1000798. 2010.... - Transcription factor regulation of CD8+ T-cell memory and exhaustionJill M Angelosanto
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Immunol Rev 236:167-75. 2010..We also discuss recent innovations in genomic and computational tools that could be used to enhance the way we understand the development of T-cell responses to infectious disease... - Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cellsAndrew M Intlekofer
Abramson Family Cancer Research Institute, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Exp Med 204:2015-21. 2007..T-bet, thus, appears to function as a molecular switch between central- and effector-memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells... - A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infectionAlison Crawford
Department of Microbiology and Institute for Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
PLoS Pathog 7:e1002098. 2011..Our results demonstrate an important role for RANTES in sustaining CD8 T cell responses during a systemic chronic viral infection... - Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virusLaurel A Monticelli
Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Nat Immunol 12:1045-54. 2011..Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus... - The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responsesAlison Crawford
Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA
Curr Opin Immunol 21:179-86. 2009..These distinct inhibitory pathways appear to cooperate in regulating T cell function, could have distinct mechanisms of action, and are likely to provide novel therapeutic targets during persisting infections and other diseases... - Cutting edge: persistently open chromatin at effector gene loci in resting memory CD8+ T cells independent of transcriptional statusValerie P Zediak
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Immunol 186:2705-9. 2011..We propose that these chromatin changes poise effector genes for rapid upregulation, but are insufficient for PolII recruitment and transcription... - Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalizationNobuhiro Nakamoto
Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Gastroenterology 134:1927-37, 1937.e1-2. 2008..As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients... - Inhibitory receptors on lymphocytes: insights from infectionsPamela M Odorizzi
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 188:2957-65. 2012..We discuss our current understanding of the molecular mechanisms for key inhibitory receptor pathways, highlight major gaps in knowledge, and explore current and future clinical applications... - K12/SECTM1, an interferon-γ regulated molecule, synergizes with CD28 to costimulate human T cell proliferationTao Wang
Molecular and Cellular Oncogenesis Program, The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19104, USA
J Leukoc Biol 91:449-59. 2012..These results indicate that SECTM1 is a broadly expressed, IFN-γ-inducible molecule, which functions as a potent costimulatory ligand for T cell activation and is synergistic with anti-CD28... - Increased programmed death-1 expression on CD4+ T cells in cutaneous T-cell lymphoma: implications for immune suppressionSara Samimi
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Arch Dermatol 146:1382-8. 2010.... - Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responsesMarcio O Lasaro
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Nat Med 14:205-12. 2008..The immunopotentiating effect required binding of the gD chimeric protein to HVEM. Overall, the studies demonstrate that targeting of antigen to the BTLA binding site of HVEM augments the immunogenicity of vaccines... - TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammationMark C Siracusa
Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Nature 477:229-33. 2011.... - CD8 T cell dysfunction during chronic viral infectionHaina Shin
Immunology Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
Curr Opin Immunol 19:408-15. 2007..In this review, we will discuss recent work that highlights two main types of T cell dysfunction during chronic infection: exhaustion of effector functions and altered memory T cell development... - A brief history of CD8 T cellsDavid Masopust
Department of Microbiology, University of Minnesota, Minneapolis, MN, USA
Eur J Immunol 37:S103-10. 2007..Herein, we recount the historical developments leading to the discovery of CD8 T cells, highlight a few of the important discoveries that have followed, and discuss some of the critical issues on the horizon... - Behavior of parasite-specific effector CD8+ T cells in the brain and visualization of a kinesis-associated system of reticular fibersEmma H Wilson
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Immunity 30:300-11. 2009....
Research Grants
- Regulation of exhaustion and altered CD8 T cell memory during chronic InfectionE John Wherry; Fiscal Year: 2010..Our studies may provide important information for the design of prophylactic vaccines and also may uncover opportunities to develop novel therapeutic interventions for chronic diseases. ..