Cytokine-Mediated Regulation of CD8 T-Cell Responses During Acute and Chronic Viral Infection

The common gamma-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, regulate critical aspects of antiviral CD8 T-cell responses. During acute infections, IL-2 controls expansion and differentiation of antiviral CD8 T cells, whereas IL-7 and IL-15 are key cytokines to maintain memory CD8 T cells long term in an antigen-independent manner. On the other hand, during chronic infections, in which T-cell exhaustion is established, precise roles of these cytokines in regulation of antiviral CD8 T-cell responses are not well defined. Nonetheless, administration of IL-2, IL-7, or IL-15 can increase function of exhausted CD8 T cells, and thus can be an attractive therapeutic approach. A new subset of stem-cell-like CD8 T cells, which provides a proliferative burst after programmed cell death (PD)-1 therapy, has been recently described during chronic viral infection. Further understanding of cytokine-mediated regulation of this CD8 T-cell subset will improve cytokine therapies to treat chronic infections and cancer in combination with immune checkpoint inhibitors.