Mechanisms underlying lineage commitment and plasticity of human yo T cells

Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, y T cells differentiate into two major types of memory T cells： central memory cells, which patrol the blood and secondary lymphoid organs, and effector memory cells, which migrate to peripheral tissues, y T cells display in vitroa certain degree of plasticity in their function that is reminiscent of that which is observed in conventional CD4 T cells. Similar to CD4 T cells, in which a plethora of specialized subsets affect the host response, y8 T cells may readily and rapidly assume distinct Thl-, Th2-, Th17-, TFH and T regulatory-like effector functions, suggesting that they profoundly influence cell-mediated and humoral immune responses. In addition to differences in cytokine repertoire, y~ T cells exhibit diversity in homing, such as migration to lymph node follicles, to help B cells versus migration to inflamed tissues. Here, we review our current understanding of y T-cell lineage heterogeneity and flexibility, with an emphasis on the human system, and propose a classification of effector y T cells based on distinct functional phenotypes.

Vitamin C as a promoter of γδ T cells

HumanγδT cells are a small CD3+subset exhibiting features of both innate and adaptive immune cell.1 The majorγδT cell population in peripheral blood expresses the Vγ9 and Vδ2 chains and recognizes phosphoantigens(PAgs)that are overexpressed by tumor cells in the absence of genetic restriction.Activation and expansion of Vγ9Vδ2 T cells is also achieved by aminobisphosphonates(n-BPs),which promote the intracellular accumulation of PAgs.Because of their potent cytotoxic and antitumor activity,Vγ9Vδ2 T cells are particularly indicated for use in cancer immunotherapy,even against tumors with low mutational burdens.

Clonal expansion shapes the human Vδ1T cell receptor repertoire

Theγδcells are a unique population of T lymphocytes that combine innate-like features and adaptive-type responses and play an important role in the early host response to infections and malignancies.Different fromαβT cells,γδT cells recognize a limited set of antigens,which are shared by a variety of microbial pathogens and tumor cells in a non-MHC restricted manner;1 thus,these cells use the TCR in a manner similar to a pattern recognition receptor(PRR).Moreover,whereasαβT cells require antigen-and cytokine-driven clonal expansion,γδT cells are equipped with immediate effector functions.1 However,the potentialγδrepertoire with junctional diversity is estimated at∼10^(18),which is much greater than theαβrepertoire(∼10^(16)),thus raising questions concerning the forces governing the selection of such a huge TCR repertoire during ontogeny and whether and how theγδTCR repertoire is shaped under physiological and pathological conditions.