Deficiency of γδ T lymphocytes contributes to mortality and immunosuppression in sepsis

Studies have indicated that gamma delta T lymphocytes play an important role in the regulation of immune function and the clearance of intracellular pathogens. We have recently reported that intraepithelial lymphocytes (IEL), which are rich in gamma delta T cells, within the small intestine illustrated a significant increase in apoptosis and immune dysfunction in mice subjected to sepsis. However, the contribution of gamma delta T cells to the host response to polymicrobial sepsis remains unclear. In this study, we initially observed that after sepsis induced by cecal ligation and puncture (CLP), there was an increase in small intestinal IEL CD8(+) gamma delta(+) T cells in control gamma delta(+/+) mice. Importantly, we subsequently found an increased early mortality in mice lacking gamma delta T cells (gamma delta(-/-) mice) after sepsis. This was associated with decreases in plasma TNF-alpha, IL-6, and IL-12 levels in gamma delta(-/-) mice compared with gamma delta(+/+) mice after sepsis. In addition, even though in vitro LPS-stimulated peritoneal macrophages showed a reduction in IL-6 and IL-12 release after CLP, these cytokines were less suppressed in macrophages isolated from gamma delta(-/-) mice. Alternatively, IL-10 release was not different between septic gamma delta(+/+) and gamma delta(-/-) mice. Whereas T helper (Th) 1 cytokine release by anti-CD3-stimulated splenocytes was significantly depressed in septic gamma delta(+/+) mice, there was no such depression in gamma delta(-/-) mice. However, gamma delta T cell deficiency had no effect on Th2 cytokine release. These findings suggest that gamma delta T cells may play a critical role in regulating the host immune response and survival to sepsis, in part by alteration of the level of IEL CD8(+) gamma delta(+) T cells and through the development of the Th1 response.