Activation of type III pneumococcal polysaccharide-specific suppressor T cells in cyclophosphamide-treated mice requirement for recognition of antigen and I-J determinants on antigen coupled to syngeneic spleen cells.
Type III pneumococcal polysaccharide (S3) coupled to spleen cells (S3-SC) is a potent tolerogen in mice. Although tolerance induced by S3-SC has been shown to be T cell dependent, T cells from tolerant mice are unable to actively suppress the antibody response to S3 when transferred to normal mice. However, when mice are given cyclophosphamide (Cy) before injection of S3-SC, suppressor T cells (Ts) are induced and can be detected by their ability to suppress the response to S3 after transfer to normal mice. The Ts induced by S3-SC in Cy-treated mice are antigen specific and can bind to and be eluted from plates coated with a soluble membrane preparation of S3-SC (S3-SCSM) prepared from mice that are syngeneic with mice in which Ts are induced. Allogeneic S3-SCSM, free S3, or S3 coupled to non-membrane carriers do not bind the Ts. Moreover, under the same conditions, detectable Ts were not induced by free S3 in either normal or Cy-treated mice. These results suggest that these Ts are activated by, and have receptors for, S3 plus a self cell membrane determinant. The self cell membrane determinant required for Ts induction is apparently I-J since Ts are induced only when the antigen-coupled spleen cells share I-J with the Cy-treated mice in which Ts are activated. The necessity to treat mice with Cy to obtain detectable Ts is presumably due to the fact that S3-SC activates a contrasuppressor T cell in normal mice which interferes with Ts function, and this cell is eliminated by Cy.
D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007116:Immunization, Passive; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011135:Polysaccharides, Bacterial; C026604:pneumococcal polysaccharide, type III; D003520:Cyclophosphamide