Suppression of Ia-unrestricted primary anti-Qa-1 cytotoxic T lymphocyte responses by class II major histocompatibility complex-restricted cellular interactions.
A model has been established for investigating the cellular interactions for the generation and regulation of primary cytotoxic T lymphocyte (CTL) responses to Qa-1 alloantigens. Although NZB anti-BALB/c one-way mixed leukocyte cultures (MLC) generate anti-Qa-1b CTL, anti-Qa-1 CTL responses are not generated during BALB/c anti-NZB one-way MLC or during two-way MLC with NZB and BALB/c spleen cells. However, depletion of L3T4+ cells from the spleens of BALB/c mice before two-way MLC with NZB spleen cells resulted in anti-Qa-1b CTL responses. Likewise, the addition of anti-L3T4 monoclonal antibody (mAb) or anti-I-Ad mAb to two-way MLC with NZB and BALB/c spleen cells resulted in the generation of anti-Qa-1b CTL. Conversely, anti-Lyt-2 mAb inhibited the generation of anti-Qa-1 CTL. These data indicate that class II major histocompatibility complex-restricted cellular interactions are capable of suppressing the generation of Ia-unrestricted anti-Qa-1 CTL responses by Lyt-2+ responder cells. This model provides a novel opportunity to both characterize the cellular interactions responsible for regulating primary CTL responses to the Qa/Tla-encoded class I molecule Qa-1, and determine the contribution of this L3T4+ Ts-dependent defect in NZB mice to the pathogenesis of autoimmunity.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D051379:Mice; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C032907:Q surface antigens