During Pneumocystis carinii pneumonia (PCP) in CD4 depleted mice, P. carinii specific CD8 T cells shift from a protective T1-type to a nonprotective and deleterious T2-type response. This detrimental response of cytotoxic T cells is further down regulated by interferon gamma and subsequent NO production. This general hypothesis will be addressed through three specific aims. First, Harmsen and colleagues will investigate the antigen specificity of CD8 T cells as they accumulate in the lungs of CD4 T cell-depleted mice during PCP. They will further investigate the role of class I MHC antigens in the activation of these cells. Next, they will determine the roles of interferon gamma and iNOS-dependent NO production in mediating the effects of CD8 T cells during PCP. Under the final aim, they will determine the mechanisms by which CD8 T cells damage the lung during PCP. They will investigate both the roles of T-cell derived perforin and recruited neutrophils in mediating this CD8 dependent lung injury.
