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 cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form 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 response to both types of antigen, indicative of a Th1 response; however, after 72h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence 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. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-gamma, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-gamma antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-gamma mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-gamma. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P. carinii infection in vivo.
Theus
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Cincinnati Veterans Affairs Medical Centre, Department of Internal Medicine, University of Cincinnati College of Medicine, OH 45220, USA.
Smulian
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Sullivan
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Walzer
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D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005656:Fungal Proteins / Q000494:pharmacology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D011010:Pneumocystis / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C077556:GPA protein, Pneumocystis carinii sp.