Lymphocytes in host defense against Pneumocystis carinii.
Host defense against Pneumocystis carinii depends on complex interactions between host immune cells and mediators. In immunocompetent hosts, the immune system provides efficient and effective defense against P. carinii. Clinical and experimental investigations confirm that lymphocytes control and coordinate this defense. During states of immunosuppression, however, lymphocyte function is impaired and clinical P. carinii pneumonia results. Lymphocytes participate in host defense by regulating other immune cells (CD4+ and CD8+ T cells), by producing antibodies against pathogens (B cells), and by killing of organisms (cytotoxic CD8+ T cells and natural killer cells). Animal models of P. carinii pneumonia, using animals with genetic or induced immunodeficiencies, have provided recent and relevant information about the roles of lymphocytes in host defense. The CD4+ T cell plays a central role in defense, and CD4+ T cells are impaired both quantitatively and qualitatively in immunosuppressed hosts. However, the mechanisms by which CD4+ T cells control defense against P. carinii require further investigation. When CD4+ T cells are unavailable for defense, CD8+ T cells can participate in defense against P. carinii, but the mechanisms of protection also remain to be determined. Although serum antibodies directed against P. carinii are ubiquitous in humans, including human immunodeficiency virus-infected individuals, recent experimental evidence shows that B cells and antibodies can contribute significantly to host defense against P. carinii. These data suggest that modulation of B cell function remains a valid approach to vaccine development. Overall, an improved understanding of lymphocytic defense against P. carinii could lead to rational development of immunotherapies directed against this important opportunistic pathogen.
Beck
J M
JM
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48105-2300, USA.
Harmsen
A G
AG
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D016867:Immunocompromised Host; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000517:prevention & control; D012680:Sensitivity and Specificity