CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in pneumocystis pneumonia in...

Pneumocystis spp. pneumonia (PCP) in humans and in surrogate animal species typically occurs in the absence of CD4 T cells, as takes place during acquired immune deficiency syndrome. However, patients treated with highly active anti-retroviral therapy sometimes exhibit an exacerbation of diseases such as PCP that coincides with resurgent CD4 T cells, a phenomenon known as immune reconstitution disease. We used an animal model of PCP using the B-cell-deficient muMT mouse together with antibody-mediated depletion of various T-cell subsets to examine the role of CD4 and CD8 T cells in the development of pathology in PCP. Although overt pathology occurs in the presence of CD4 T cells only, CD8 T cells only, or both, pulmonary injury occurs via different paths, depending on the complement of T cells present. Surprisingly, profound damage occurred when only CD4 T cells were present, and this pathology coincided with enhanced recruitment and activation of eosinophils and strong type 2 cytokine polarization in the alveolar environment. In addition, CD8 T cells can act to moderate this CD4 T cell-mediated pathology, possibly by increasing the ratio of putative CD25+ suppressor CD4 T cells to CD25- effector CD4 T cells.