Krüppel-like factor 2 regulates trafficking and homeostasis of gammadelta T cells.

gammadelta T cells are generated in the thymus and traffic to secondary lymphoid organs and epithelial surfaces, where they regulate immune responses. alphabeta T cells require sphingosine 1-phosphate receptor type 1 (S1P(1)) and CD62L for thymic emigration and circulation through secondary lymphoid organs. Both of these genes are regulated by the transcription factor Krüppel-like factor 2 (KLF2) in conventional alphabeta T cells. It is unclear if gammadelta T cells use similar mechanisms. In this study, we show that thymic gammadelta T cells express S1P(1) and that it is regulated by KLF2. Furthermore, KLF2 and S1P(1)-deficient gammadelta T cells accumulate in the thymus and fail to populate the secondary lymphoid organs or gut, in contrast to the expectation from published work. Interestingly, KLF2 but not S1P(1) deficiency led to the expansion of a usually rare population of CD4(+) promyelocytic leukemia zinc finger(+) "gammadelta NKT" cells. Thus, KLF2 is critically important for the homeostasis and trafficking of gammadelta T cells.