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

• Published in: Clinical and experimental immunology Vol. 85; no. 1; pp. 55 - 60
• Main Authors: SAKANE, T., MURAKAWA, Y., TAKENO, M., SHIGEKI, T., NAGAFUCHI, H., MIKI, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1991; Blackwell
• Subjects: Adult; Aged; Antibodies, Monoclonal - immunology; Arthritis, Rheumatoid - immunology; autologous mixed lymphocyte reaction; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8+ T cells; Cell Adhesion Molecules - immunology; Diseases of the osteoarticular system; Female; Humans; Inflammatory joint diseases; L-Selectin; Leu8 antigen; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Male; Medical sciences; Middle Aged; rheumatoid arthritis; T cell activation cascade; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; Human; Cell proliferation; Immunopathology; Mixed lymphocyte reaction; Pathogenesis; Diseases of the osteoarticular system; Autoimmune disease; Activation; Inflammatory joint disease; Autologous system; Cell subpopulation; Rheumatoid arthritis; T-Lymphocyte
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1991.tb05681.x

SUMMARY 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.