T cell interactions in active rheumatoid arthritis: insights from the human autologous mixed lymphocyte reaction as a model of T cell activation cascade

Abstract

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4⁺ and CD8⁺ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4⁺ Leu8⁺ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4⁺ Leu8^- cells and CD8⁺ Lcu8⁺ cells. The activated CD8⁺Lcu8⁺ cells, in turn, induce CD8⁺ Leu8^- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8⁺ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8⁺ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8⁺ T cell function may contribute to the pathogenesis of the disease.