Obesity Impairs γδT Cell Homeostasis and Antiviral Function in Humans

Obese patients are susceptible to increased morbidity and mortality associated with infectious diseases such as influenza A virus gamma delta T cells and memory alpha beta T cells play key roles in reducing viral load by rapidly producing IFN-gamma and lysing infected cells. In this article we analyze the impact of obesity on T lymphocyte antiviral immunity. Obese donors exhibit a reduction in gamma delta T cells in the peripheral blood. The severity of obesity negatively correlates with the number of gamma delta T cells. The remaining gamma delta T cells have a skewed maturation similar to that observed in aged populations. This skewed gamma delta T cell population exhibits a blunted antiviral IFN-gamma response. Full gamma delta T cell function can be restored by potent stimulation with 1-Hydroxy- 2-methyl-buten-4yl 4-diphosphate (HDMAPP), suggesting that gamma delta T cells retain the ability to produce IFN-gamma. Additionally, gamma delta T cells from obese donors have reduced levels of IL-2R alpha. IL-2 is able to restore gamma delta T cell antiviral cytokine production, which suggests that gamma delta T cells lack key T cell specific growth factor signals. These studies make the novel finding that the gamma delta T cell antiviral immune response to influenza is compromised by obesity. This has important implications for the development of therapeutic strategies to improve vaccination and antiviral responses in obese patients.