Role of KLFs in T-cell development, activation, and trafficking. In response to activation of TCR signaling, KLF2 expression is reduced, whereas the immunomodulatory drugs “statins” and rapamycin increase KLF2 expression. KLF2 is required for: (1) maintaining the quiescent state of single-positive CD4⁺ or CD8⁺ T cells; (2) induction of T-cell trafficking markers S1P1, CD62L, β7-integrin on thymic CD4⁺ T cells to allow for egress into peripheral lymphoid tissues; and (3) expression of chemokine receptors, such as CCR3, CCR5, and CXCR3, by autonomously or nonautonomously regulating levels of IL-4 in CD8⁺ T cells. The Ets transcription factor ELF activates KLF4 expression to negatively regulate naive CD8⁺ T-cell proliferation and induces KLF2 to promote T-cell homing. In response to TGF-β1, KLF10 expression is induced and promotes Treg cell differentiation by targeting both TGF-β1 and Foxp3 as part of a positive feedback loop; in contrast, KLF10 inhibits Th1 and Th2-mediated pathways. KLF10 also promotes Treg cell suppressor function independent of Foxp3 by increasing the expression of TGF-β1 in Tregs.