No abstract

When kept under strict specific-pathogen-free conditions, H-2I-A␤ (A␤ ؊/؊), T-cell receptor ␤ (TCR␤ ؊/؊), and recombinase-activating gene 1 (RAG-1 ؊/؊) gene disruption mutant mice, deficient in conventional CD4 ؉ T cells, TCR␣␤ cells, and all peripheral T and B lymphocytes, respectively, consistently developed lethal Pneumocystis carinii pneumonia through natural infection. The most severe symptoms appeared in RAG-1 ؊/؊ mutants. In contrast, TCR␦ ؊/؊ and ␤ 2-microglobulin ؊/؊ (␤ 2 m ؊/؊) mutants, deficient in TCR␥␦ cells and conventional CD8␣␤ ؉ TCR␣␤ cells, respectively, were fully resistant to infection. Our data indicate not only the insufficiency but also the dispensability of CD8␣␤ ؉ TCR␣␤ cells and of TCR␥␦ lymphocytes in resistance to P. carinii infection. Under disease conditions, large numbers of unusual single-positive CD4 ؉ and CD8␣␤ ؉ as well as double-negative TCR␥␦ subpopulations of cells accumulated in lungs of TCR␤ ؊/؊ mutants. This accumulation was consistently accompanied by a drastic increase in the pulmonary B-cell population. In contrast, CD8␣␤ ؉ TCR␣␤ cells, but no B cells, appeared in lungs of parasitized A␤ ؊/؊ mutants. Since lung damage and parasite numbers were less prominent in morbid TCR␤ ؊/؊ and A␤ ؊/؊ mutants than in diseased RAG-1 ؊/؊ mice, the remaining lymphocytes accumulating in lungs of the former two mutants seem to perform residual resistance functions.

No abstract

Resistance to Pneumocystis carinii is achieved through cell-mediated and humoral immunity, but the interplay between these two systems in the immunocompetent host is not fully understood. TCRbetaxdelta-/- double-mutant mice deficient of all T cell populations naturally acquired P. carinii pneumonia with lethal consequences. Moribund mutants displayed numbers of pulmonary pathogens comparable to RAG-1-/- mice lacking all functional T and B lymphocytes. Pulmonary lavage cells of diseased TCRbetaxdelta-/- mutants secreted proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-12, and interferon-gamma, but not IL-4, -5, or -10. Serum immunoglobulin 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 strict T cell dependence of immunoglobulin switching to this isotype. Other IgG subclasses were strongly reduced and did not bind P. carinii. These results suggest that T cells are crucial for generation of antibodies against P. carinii relevant to resistance.