Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 95, Issue 5, Pages 705-713Publisher
WILEY
DOI: 10.1189/jlb.0813429
Keywords
memory; cytokines; STAT4; LCMV; Tbet; effector
Categories
Funding
- U.S. National Institutes of Health [R01 DK084082, T32 AI07051, R01 AI04360, U01 AI082966]
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Effector and memory CD4 and CD8 T cell responses are critical for the control of many intracellular pathogens. The development of these populations is governed by transcription factors that molecularly control their differentiation, function, and maintenance. Two transcription factors known to be involved in these processes are Tbet and STAT4. Although Tbet has been shown to regulate CD8 T cell fate decisions and effector CD4 T cell choices, the contribution of STAT4 is less well understood. To address this, we examined the impact of STAT4 on T cell responses in the presence or absence of Tbet, following LCMV infection by using mice lacking Tbet, STAT4, or both transcription factors. STAT4 was not required for Tbet or Eomes expression; however, virus-specific effector CD8 T cells are skewed toward a memory-precursor phenotype in the absence of STAT4. This altered proportion of memory precursors did not result in an increase in memory CD8 T cells after the resolution of the infection. We also demonstrate that virus-specific effector and memory CD4 T cells formed independently of Tbet and STAT4, although a slight reduction in the number of antigen-specific CD4 T cells was apparent in mice lacking both transcription factors. Collectively, we have discovered distinct roles for Tbet and STAT4 in shaping the phenotype and function of virus-specific T cell responses. Tbet and STAT4 have distinct roles in effector T cell differentiation, but are not required for generation of T cell memory.
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