An essential role for gamma delta T cells in pathogen protection

gammadelta T cells are a minor population of the circulating pool of lymphocytes with unique receptor characteristics and effector potential. These cells have features of both the innate and adaptive immune systems, sharing many of the functional capacities of conventional adaptive immune cells but with the response kinetics, location and directed receptor specificities predicted for innate cells. Based on their intermediate phenotype we hypothesized that gammadelta T cells would play an essential role in infections requiring a robust early response for pathogen clearance and survival.; Using the model system of gram-negative bacterial pneumonia, we determined that gammadelta T cells do mediate important effects in the host immune response. Following challenge with either Klebsiella pneumoniae or Pseudomonas aeruginosa, gammadelta T cell deficient mice had increased mortality. In wild type controls, gammadelta T cells were recruited to the site of infection and produced the proinflammatory cytokine IL-17. Further, a significant portion of the recruited cells expressed T cell receptors specific for a self-ligand induced following infection. These data implicate gammadelta T cells in the pathogen-appropriate proinflammatory response that mediates clearance and survival.; To further test the hypothesis that a gammadelta T cell effect would be specific to fulminant infectious processes, we tested their role following infection with an isogenic mutant of Pseudomonas aeruginosa with greatly decreased virulence. In this system, gammadelta T cell deficiency was not associated with increased susceptibility and it was not possible to observe recruitment of the cells to the lungs following bacterial challenge. These findings suggest that gammadelta T cell activation, here demonstrated to involve host molecules induced by microbial challenge, may be restricted to cases of severe infection associated with host tissue damage.; Clinically, pneumonia remains a significant cause of mortality and the studies presented here offer some direction for investigations into immunomodulators that may promote host defenses and enhance survival.