γδ T Cells in Immunoregulation
The regulatory function of γδ T cells has not been appreciated until recently. In murine epithelial tissues, dendritic epidermal γδ T cells (DETCs) play a critical regulatory function in skin tissue surveillance and wound repair. It has been shown that this process is mediated by direct lyses of stressed or damaged keratinocytes via a cell-cell contact dependent mechanism. DETC-derived cytokines such as keratinocyte growth factor-1/2 and insulin-like growth factor-1 have also involved in regulating the processes of tissue repair, keratinocyte proliferation and survival, migration and recruitment of inflammatory cells. Moreover, DETCs can directly down-regulate cutaneous inflammation, promote wound healing, and protect against cutaneous malignancy. In humans, Vδ1 cells in tumor-infiltrating lymphocytes (TIL) from human breast cancer have been shown to possess an inhibitory effect on αβ T cells and dendritic cells in a soluble factor-dependent manner. Such immunosuppressive activity could be reversed by human Toll-like receptor 8 ligands both in-vitro and in-vivo, indicating that a unique TLR8 signaling pathway is involved in suppression of regulatory γδ1 TILs. More questions regarding the regulatory functions and the mechanism of suppression of γδ T cells need to be addressed in future studies, and these answers may have important implications in γδ T cell-based adoptive therapy for the treatment of cancers in clinic.
KeywordsTumor Immunity Cutaneous Inflammation Adoptive Therapy Skin Organ Culture Intestinal Intraepithelial Lymphocyte
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