NATURALLY ACQUIRED PNEUMOCYSTIS-CARINII PNEUMONIA IN GENE DISRUPTION MUTANT MICE - ROLES OF DISTINCT T-CELL POPULATIONS IN INFECTION

When kept under strict specific-pathogen-free conditions, H-2I-A beta (A beta(-/-)), T-cell receptor beta (TCR beta(-/-)), and recombinase-a ctivating gene 1 (RAG-1(-/-)) gene disruption mutant mice, deficient i n conventional CD4(+) T cells, TCR alpha beta cells, and all periphera l T and B lymphocytes, respectively, consistently developed lethal Pne umocystis carinii pneumonia through natural infection. The most severe symptoms appeared in RAG-1(-/-) mutants. In contrast, TCR delta(-/-) and beta(2)-microglobulin(-/-) (beta(2)m(-/-)) mutants, deficient in T CR gamma delta cells and conventional CD8 alpha beta(+) TCR alpha beta cells, respectively, were fully resistant to infection. Our data indi cate not only the insufficiency but also the dispensability of CD8 alp ha beta(+) TCR alpha beta cells and of TCR gamma delta lymphocytes in resistance to P. carinii infection, Under disease conditions, large nu mbers of unusual single-positive CD4(+) and CD8 alpha beta(+) as well as double-negative TCR gamma delta subpopulations of cells accumulated in lungs of TCR beta(-/-) mutants. This accumulation was consistently accompanied by a drastic increase in the pulmonary B-cell population. In contrast, CD8 alpha beta(+) TCR alpha beta cells, but no B cells, appeared in lungs of parasitized A beta(-/-) mutants. Since lung damag e and parasite numbers were less prominent in morbid TCR beta(-/-) and A beta(-/-) mutants than in diseased RAG-1(-/-) mice, the remaining l ymphocytes accumulating in lungs of the former two mutants seem to per form residual resistance functions.