Innate-like CD27CD45RB γδ T Cells Require TCR Signaling for Homeostasis in Peripheral Lymphoid Organs.

TCR signaling is required for homeostasis of naive αβ T cells. However, whether such a signal is necessary for γδ T cell homeostasis in the periphery remains unknown. In this study, we present evidence that a portion of Vγ2 γδ T cells, one of the major γδ T cell subsets in the secondary lymphoid organs, requires TCR signaling for homeostasis. To attenuate γδTCR signals, we generated mice lacking Eγ4 (Eγ4), an enhancer located at the 3'-most end of the TCRγ locus. Overall, we found that in thymus, Eγ4 loss altered V-J rearrangement, chromatin accessibility, and transcription of the TCRγ locus in a distance-dependent manner. Vγ2 γδ T cells in Eγ4 mice developed normally both fetal and adult mouse thymi but were relatively reduced in number in spleen and lymph nodes. Although Vγ2 TCR transcription decreased in all subpopulations of Eγ4 mice, the number of Vγ2 γδ T cells decreased and TCR signaling was attenuated only in the innate-like CD27CD45RB subpopulation in peripheral lymphoid organs. Consistently, CD27CD45RB Vγ2 γδ T cells from Eγ4 mice transferred into Rag2-deficient mice were not efficiently recovered, suggesting that continuous TCR signaling is required for their homeostasis. Finally, CD27CD45RB Vγ2 γδ T cells from Eγ4 mice showed impaired TCR-induced activation and antitumor responses. These results suggest that normal homeostasis of innate-like CD27CD45RB Vγ2 γδ T cells in peripheral lymphoid organs requires TCR signaling.