Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory

PLoS Pathogens

Varun N. Kapoor¹  M. Suresh¹  Peng Li¹  E. John Wherry²  Liisa K. Selin³  Susan M. Kaech⁴  Hyun Mu Shin⁵  Gwanghun Kim⁵  Leslie J. Berg⁵  Warren J. Leonard⁵  Raymond M. Welsh⁶  Hang-Rae Kim⁶ 

[1] Department of Anatomy and Cell Biology, Department of Biomedical Sciences, and BK21Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America;Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School Medicine, Philadelphia, Pennsylvania, United States of America;Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Dept of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland, United States of America

关键词: T cells;    Cytotoxic T cells;    Memory T cells;    Cytokines;    Gene regulation;    Chromatin immunoprecipitation;    Gene expression;    Transcription factors;   

DOI  :  10.1371/journal.ppat.1006544

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8+ T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32-/- mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8+ T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8+ effector T cells that is required for the balanced regulation of effector versus memory responses to infection.

【 授权许可】

CC BY