Serologic responses to Pneumocystis carinii antigens in health and disease.

Serum antibodies to human Pneumocystis carinii antigens were measured in greater than 400 specimens from different population groups by the immunoblotting technique. Serologic responses varied during the first 2 years of life, but in children greater than or equal to 2 1/2 years and in adults antibodies to a 40-kDa band were found in greater than 85% of the specimens; antigens to bands of 66, 92, and 116 kDa were also detected frequently. The prevalence of serum antibodies in immunosuppressed patients varied at different institutions and was usually lower than that of healthy controls. Seven (41%) of 17 patients with single episodes of pneumocystosis and 13 (93%) of 14 patients with recurrent episodes followed sequentially developed active serum IgM and/or IgG antibody responses to the 40-kDa antigen. Serologic responses to P. carinii were also detected, though less frequently, by immunofluorescence. These data suggest that the 40-kDa antigen is a major marker of P. carinii infection and that immunoblotting is useful in measuring serum antibody responses to the organism in both normal and immunocompromised hosts.

Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice.

Outbreaks of Pneumocystis carinii pneumonia occurred in colonies of nu/nu and scid/scid mice at four different institutions. The disease, which was characterized by chronic wasting and respiratory insufficiency, was more severe in older mice and in animals housed in cages with special protective tops. Histopathologic features included alveolar filling with the typical foamy honeycomb material and a mild, nonspecific host inflammatory response. Immunofluorescence and immunoblotting studies suggested the P. carinii isolate was of mouse rather than of rat or human origin, and the outbreaks could be related to each other by common vendor or source of breeding animals. Once P. carinii became established in a mouse colony, the organism tended to persist for long periods of time. The principal control measure was depopulation of the colony, although limited experience with the administration of trimethoprim-sulfamethoxazole was encouraging. Thus, outbreaks of pneumocystosis are a serious problem among colonies of immunodeficient mice, with important implications for the use of these animals in biomedical research. Data obtained by studying these outbreaks should enhance understanding of the pathogenesis of P. carinii pneumonia and be helpful in formulating improved methods of detection and control.

Blastogenic responses to Pneumocystis carinii among patients with human immunodeficiency (HIV) infection.

Proliferative responses by human peripheral blood mononuclear cells and rat spleen cells were measured to Pneumocystis carinii in a blastogenic assay using organisms obtained from rat lungs and propagated in tissue culture as the antigen. Responses occurred only in subjects with known prior exposure to P. carinii and the magnitude of the response varied with the number of organisms present in the antigen preparation and days in culture. Healthy human adults showed higher proliferative responses to P. carinii than did patients with Class II (asymptomatic) or Class III (lymphadenopathy) human immunodeficiency virus (HIV) infection. No responses to the preparation were found among Class IV HIV patients with the acquired immunodeficiency syndrome, including those with prior episodes of P. carinii pneumonia or those receiving azidothymidine. Overall, the blastogenic responses obtained with P. carinii were similar to those obtained with tetanus toxoid and phytohemagglutinin, and correlated well with the number of circulating CD4 cells. The data suggest that the blastogenic assay using tissue culture-derived rat P. carinii is specific for the organism and should be helpful in studying the cellular immune responses in pneumocystosis among different human patient populations.