CYTOKINE RESPONSES TO THE NATIVE AND RECOMBINANT FORMS OF THE MAJOR SURFACE GLYCOPROTEIN OF PNEUMOCYSTIS-CARINII

Pneumocystis carinii is a major opportunistic pathogen and leading cau se of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encod ed by unique genes, is highly immunogenic and contains T cell-protecti ve epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant f orm of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-gamma) in respons e to both types of antigen, indicative Of a Th1 response; however, aft er 72h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the prese nce of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-gamma and elevated levels of IL-4. Interes tingly, cells incubated with MSG-B and IL-4 reduced production of IFN- gamma, but were not stimulated to produce increased levels of IL-4. Th e presence of anti-IFN-gamma antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-gamma mRNA, suggesting t hat the generation of Th1 cells in response to MSG or MSG-B was not de pendent on IFN-gamma. We conclude that native MSG, which contains mult iple forms of this antigen, and recombinant MSG-elicit different cytok ine responses in vitro. These data are not only important to studies o f MSG, but may also be relevant to the role of MSG in the immunopathog enesis of P. carinii infection in vivo.