Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors.
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.
Departments of Cell, Developmental, and Integrative Biology.
Sarah B
SB
Mollo
Biology, and.|Microbiology, University of Alabama at Birmingham, Alabama, USA.
Jennifer T
JT
Ingram
Departments of Cell, Developmental, and Integrative Biology.
Robert L
RL
Kress
Microbiology, University of Alabama at Birmingham, Alabama, USA.
Allan J
AJ
Zajac
Departments of Cell, Developmental, and Integrative Biology, lharring@uab.edu.
Laurie E
LE
Harrington
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050797:STAT4 Transcription Factor / Q000172:deficiency* / Q000276:immunology; D020825:T-Box Domain Proteins / Q000172:deficiency* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
LCMV; STAT4; Tbet; cytokines; effector; memory