Pneumocystis carinii pneumonia in mutant mice deficient in both TCR alpha beta and TCR gamma delta cells: Cytokine and antibody responses

Resistance to Pneumocystis carinii is achieved through cell-mediated and hu moral immunity, but the interplay between these two systems in the immunoco mpetent host is not fully understood. TCR beta x delta(-/-) double-mutant m ice deficient of all T cell populations naturally acquired P. carinii pneum onia with lethal consequences. Moribund mutants displayed numbers of pulmon ary pathogens comparable to RAG-1(-/-) mice lacking all functional T and B lymphocytes. Pulmonary lavage cells of diseased TCR beta x delta(-/-) mutan ts secreted proinflammatory cytokines tumor necrosis factor-alpha, interleu kin (IL)-12, and interferon-gamma, but not IL-4, -5, or -10. Serum immunogl obulin levels of both healthy and diseased mice were significantly reduced compared with immunocompetent animals. Secreted antibodies were mainly IgM, which also bound P. carinii. Mutants completely lacked IgG1, emphasizing s trict T cell dependence of immunoglobulin switching to this isotype. Other IgG subclasses were strongly reduced and did not bind P. carinii. These res ults suggest that T cells are crucial for generation of antibodies against P. carinii relevant to resistance.