MEMORY CD4+T CELLS ARE REQUIRED FOR OPTIMAL NK CELL EFFECTOR FUNCTIONS AGAINST THE OPPORTUNISTIC FUNGAL PATHOGEN PNEUMOCYSTIS MURINA

摘要

Little is known about the role of NK cells or their interplay with other immune cells during opportunistic infections. Using our murine model of Pneumocystis pneumonia, we found that loss of NK cells during immunosuppression results in substantial Pneumocystis lung burden. During early infection of C57B/6 CD4⁺ T cell depleted mice, there were significantly less NK cells in the lung tissue compared to CD4⁺ T cell intact animals, and the NK cells present demonstrated decreased upregulation of the activation marker NKp46 and production of the effector cytokine, IFN-γ. Furthermore, co-incubation studies revealed a significant increase in fungal killing when NK cells were combined with CD4⁺ T cells compared to either cell alone which was coincident with a significant increase in perforin production by NK cells. Finally, however, we found through adoptive transfer that memory CD4⁺ T cells are required for significant NK cell upregulation of the activation marker NKG2D and production of IFN-γ, granzyme B and perforin during Pneumocystis infection. To the best of our knowledge, this study is the first to not only demonstrate a role for NK cells in immunity to Pneumocystis pneumonia, but also to establish a functional relationship between CD4⁺ T cells and NK cells in the host response to an opportunistic fungal pathogen.