Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory.
Hyun Mu ShinVarun N KapoorGwanghun KimPeng LiHang-Rae KimM SureshSusan M KaechE John WherryLiisa K SelinWarren J LeonardRaymond M WelshLeslie J BergPublished in: PLoS pathogens (2017)
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.
Keyphrases
- transcription factor
- induced apoptosis
- regulatory t cells
- working memory
- dendritic cells
- cell cycle arrest
- type iii
- poor prognosis
- sars cov
- endoplasmic reticulum stress
- dna binding
- type diabetes
- stem cells
- gene expression
- single cell
- risk assessment
- oxidative stress
- immune response
- blood brain barrier
- brain injury
- disease virus
- cerebral ischemia
- bioinformatics analysis