Evidence for regulation of the autoimmune anti-erythrocyte response by idiotype specific suppressor T cells in NZB mice

Abstract

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 idiotype (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-binding cells is comparable with that obtained after generalized depletion of Ts by treatment with anti-CD8 + C, suggesting that the G-8-binding 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 allotype specific, nor do they appear to have MRBC antigens bound to or expressed on their membranes. Rather, these cells are more likely G-8 idiotype specific. The regulatory G-8-binding cells are CD8+ T cells, not B cells. Furthermore, Ts-enriched populations when depleted of G-8-binding 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-positive NZB mice.(ABSTRACT TRUNCATED AT 250 WORDS)