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The fate of T cells differentiating into the CD4 or CD8 lineage is typically fixed when cells leave the thymus. However, CD4+ helper T cells can be reprogrammed to develop into CD4+CD8α+ cytotoxic T lymphocytes in the gut.
The Nr4a family of transcription factors transactivate expression of the transcription factor Foxp3 and are essential for the generation of regulatory T cells. Mice deficient in all three members of the Nr4a family develop massive multiorgan inflammation.
Severe intestinal pathology associated with infection with Toxoplasma gondii is a result of the loss of Paneth cells, an unexpected side effect of the secretion of IFN-γ by protective CD4+ T cells in the intestinal mucosa.
Maintenance of the peripheral naive CD8+ T cell pool depends on T cell antigen receptor (TCR) signals and interleukin 7 (IL-7). TCR signaling limits the duration of IL-7 signals to avoid an interferon-γ-mediated mechanism of apoptotic death of naive CD8+ T cells.
Double-negative (DN) thymocytes depend on interleukin 7 (IL-7) for survival. In DN2 and DN3 cells, a new role has now been identified for signaling via the IL-7 receptor and the kinase Jak3 that leads to noncanonical activation of the transcription factor NFATc1 and upregulation of expression of the antiapoptotic protein Bcl-2.
Signaling via the complement factors C3a and C5a regulates effector T cell responses. Evidence now links the absence of local complement activation with a default pathway that leads to the polarization of Foxp3+ regulatory T cells.
