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- Title
Transient expression of ZBTB32 in anti-viral CD8<sup>+</sup> T cells limits the magnitude of the effector response and the generation of memory.
- Authors
Shin, Hyun Mu; Kapoor, Varun N.; Kim, Gwanghun; Li, Peng; Kim, Hang-Rae; Suresh, M.; Kaech, Susan M.; Wherry, E. John; Selin, Liisa K.; Leonard, Warren J.; Welsh, Raymond M.; Berg, Leslie J.
- Abstract
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.
- Subjects
T cells; VIRUS diseases; TRANSCRIPTION factors; CD8 antigen; CELL proliferation
- Publication
PLoS Pathogens, 2017, Vol 13, Issue 8, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1006544