Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity.
The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. We found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, we utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus.
H
H
Golding
T I
TI
Munitz
A
A
Singer
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D011828:Radiation Chimera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D000939:Epitopes; D000949:Histocompatibility Antigens Class II