A comparative view on vitamin C effects on αβ- versus γδ T-cell activation and differentiation

Vitamin C (VitC) is an essential vitamin that needs to be provided through exogenous sources. It is a potent anti-oxidant, and an essential cofactor for many enzymes including a group of enzymes that modulate epigenetic regulation of gene expression. Moreover, VitC has a significant influence on T-cell differentiation, and can directly interfere with T-cell signaling. Conventional CD4 and CD8 T cells express the alpha beta TCR and recognize peptide antigens in the context of MHC presentation. The numerically small population of gamma delta T cells recognizes antigens in an MHC-independent manner. gamma delta T cells kill a broad variety of malignant cells, and because of their unique features, are interesting candidates for cancer immunotherapy. In this review, we summarize what is known about the influence of VitC on T-cell activation and differentiation with a special focus on gamma delta T cells. The known mechanisms of action of VitC on alpha beta T cells are discussed and extrapolated to the effects observed on gamma delta T-cell activation and differentiation. Overall, VitC enhances proliferation and effector functions of gamma delta T cells and thus may help to increase the efficacy of gamma delta T cells applied as cancer immunotherapy in adoptive cell transfer.