Krüppel-Like Factor 2 Regulates Trafficking and Homeostasis of γδ T Cells

Abstract

γδ T cells are generated in the thymus and traffic to secondary lymphoid organs and epithelial surfaces, where they regulate immune responses. αβ T cells require sphingosine 1-phosphate receptor type 1 (S1P1) 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 αβ T cells. It is unclear if γδ T cells use similar mechanisms. In this study, we show that thymic γδ T cells express S1P1 and that it is regulated by KLF2. Furthermore, KLF2 and S1P1-deficient γδ 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 S1P1 deficiency led to the expansion of a usually rare population of CD4+ promyelocytic leukemia zinc finger+ “γδ NKT” cells. Thus, KLF2 is critically important for the homeostasis and trafficking of γδ T cells.