Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factors (P6052)

Abstract

Abstract The eradication of various types of pathogens is mediated by the coordinated efforts of both effector CD4 and CD8 T cells. Following pathogen control, the majority of CD4 and CD8 T cell effector populations undergo apoptosis, but a subset of these cells persists, giving rise to the memory T cell pool. The requirements for the generation of T cell memory have not been completely elucidated, hence we were interested in understanding importance of the Th1 transcription factors Tbet and STAT4 in this process. To interrogate this, we utilized lymphocytic choriomeningitis virus infection of BALB/c mice. Not surprisingly, we observed that in the absence of Tbet, the virus-specific CD4 T cell IFNγ response was ablated but the IL-2 response remained unperturbed. In contrast, we found that STAT4 was not required for IFNγ production by virus-specific CD4 T cells. Conversely, the functional virus-specific CD8 T cell response was intact in the absence of Tbet, STAT4, or both, although increases in the proportion of effector cells competent for IL-2 production were noted in mice that lacked Tbet expression. We did detect marked differences in the expression of CD127 and KLRG1 on virus-specific effector CD8 T cells, however this did not translate into alterations in the numbers of memory CD8 T cells after the resolution of the infection. Collectively, we discovered distinct roles for Tbet and STAT4 in shaping the phenotype and function of virus-specific T cell responses.