International Immunology, Vol. 2, No. 2, pp. 127-133,February 1990
© 1990 Japanese Society for Immunology
Evidence for regulation of the autoimmune anti-erythrocyte response by idiotype specific suppressor T cells in NZB mice
Department of Microbiology, Thomas Jefferson University Philadelphia, PA, USA
2 Department of Immunology and Cancer, Research Institute of the Cleveland Clinic Foundation Cleveland, OH, USA
Correspondence to: Correspondence to. C. E. Calkins, Department of Microbiology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA
Correspondence to: 1Present address Medical Biology Institute, La Jolla, CA 92037, USA
The present study demonstrates that specific CD8+ CD4– suppressor T cells (Ts) actively regulate the autoimmune anti-mouse red blood cell (MRBC) antibody response in spleen cell populations of young, Coombs-negative NZB mice. These Ts appear to bind a monoclonal NZB autoantibody (G-8 mAb) to unmodified MRBC which expresses a dominant idlotype (Id) in the spontaneous anti-MRBC autoantibody response of NZB mice. Treatment of normally nonauto responsive spleen cells from young NZB mice with the G-8 mAb + C prior to culture allows these cells to develop, in 4-5 days, an autoantibody response to MRBC. The level of response obtained after depletion of the G-8-blndlng cells is comparable with that obtained after generalized depletion of Ts by treatment with antl-CD8 + C, suggesting that the G-8-blndlng cells make up a major portion of the regulatory Ts in this response. Yet, G-8 + C treatment depletes a very small subset of cells and not the total CD8+ T cell population. The regulatory cells appear to be neither isotype nor aliotype specific, nor do they appear to have MRBC antigens bound to or expressed on their membranes. Rather, these cells are more likely G-8 Idlotype specific. The regulatory G-8-binding cells are CD8+ T cells, not B cells. Furthermore, Ts-enriched populations when depleted of G cells lose their ability to suppress In vitro anti-MRBC responses of spleen cells from Coombs-negative NZB mice depleted of CD8+ cells, as well as those of unfractionated spleen cells from Coombs-posltlve NZB mice. The data presented support the hypothesis that the NZB anti-MRBC autoantibody response is regulated In young (‘preautoimmune") mice by G-8 Idiotype specific Ts.
Keywords: idiotype-specific suppressor T cells, self-tolerance, autoimmunity, Coombs positivity
Received 23 August 1989, accepted 9 October 1989.
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