title: Murine CD8+ T suppressors against mycobacterial 65-kDa antigen compete for IL-2 and show lack of major histocompatibility complex-imposed restriction specificity in antigen recognition.
abstract: The mechanism of antigen-specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T suppressor cell (Ts) of M. vaccae-primed mice recognized the 65-kDa antigen of the bacillus, presented by I-A and I-E, respectively. The CD8+ Ts could inhibit non-antigen-specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)-2 (concanavalin A-stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65-kDa antigen. The degree of inhibition was dependent upon the amount of added IL-2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen-presenting cells, and the 65-kDa antigen, the primed CD8+ T cells absorbed IL-2 as efficiently as primed CD4+ T cells. Based on this, it was concluded that the primed CD8+ T cells induced suppression by competition for IL-2. Employing the same model, the MHC restriction of recognition of the suppressor epitope of the 65-kDa antigen by the CD8+ Ts was investigated. The epitopes presented by diverse MHC class II molecules, such as self I-A, I-E and even allogeneic I-E were similar, because they were recognized by the same population of primed CD8+ Ts. Further, immunization of C57BL/6 mice with Ltk-cells expressing H-2 DkKk alloantigens, stimulated CD8+ T cells capable of recognizing M.vaccae 65-kDa antigen. Based on these data, it was proposed that recognition of the suppressor epitope of the 65-kDa antigen by the primed CD8+ Ts exhibits lack of restriction specificity imposed by MHC diversity.
authors.affiliation: Department of Immunology, Haffkine Institute, Parel, Bombay, India.
authors.forename: S
authors.initials: S
authors.lastname: Khetan
authors.forename: K B
authors.initials: KB
authors.lastname: Sainis
authors.forename: S
authors.initials: S
authors.lastname: Rath
authors.forename: R
authors.initials: R
authors.lastname: Kamat
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000737:chemistry; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009161:Mycobacterium / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2