Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity

Sharpe and colleagues review salient aspects of CD8(+) T cell dysfunction in cancer, chronic viral infections and autoimmunity, with a view of developing new ways to alleviate T cell exhaustion and enhance CD8(+) T cell functions in cancer and chronic viral infection, as well as strategies to induce or augment exhaustion-like features to treat autoimmunity. CD8(+) T cells are critical mediators of cytotoxic effector function in infection, cancer and autoimmunity. In cancer and chronic viral infection, CD8(+) T cells undergo a progressive loss of cytokine production and cytotoxicity, a state termed T cell exhaustion. In autoimmunity, autoreactive CD8(+) T cells retain the capacity to effectively mediate the destruction of host tissues. Although the clinical outcome differs in each context, CD8(+) T cells are chronically exposed to antigen in all three. These chronically stimulated CD8(+) T cells share some common phenotypic features, as well as transcriptional and epigenetic programming, across disease contexts. A better understanding of these CD8(+) T cell states may reveal novel strategies to augment clearance of chronic viral infection and cancer and to mitigate self-reactivity leading to tissue damage in autoimmunity.