Functional Significance of Anti-T-Lymphocyte Antibodies in Sarcoidosis

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Abstract
Pulmonary sarcoidosis is a chronic disorder characterized by the activation of helper/inducer T-cells in the lung without a concomitant increase in suppressor/cytotoxic T-cells. It is known that patients with sarcoidosis have circulating anti-T-cell antibodies, primarily of the IgM class. To evaluate a functional role for these antibodies in enhancing lung helper T-cell processes in pulmonary sarcoidosis, we evaluated serum and lavage fluid of patients with active sarcoidosis for the presence of anti-T-cell antibodies, the T-cell subset specificity of these antibodies, and the possible stimulatory or inhibitory effects of these antibodies on T-cells relevant to the exaggerated helper T-cell processes in sarcoidosis. Indirect immunofluorescence studies demonstrated that sarcoid patients had anti-T-cell antibodies of the IgM type reacting with autologous as well as with nonautologous normal T-cells. IgM recovered in sarcoid lavage fluid also reacted with T-cells, thus demonstrating the autoantibodies at the site of disease. Two-color immunofluorescence and flow cytometry showed that these sarcoid autoantibodies bound to mostly Leu2+ suppressor/cytotoxic T-cells, but also to a small proportion of Leu3+ helper/inducer T-cells. Incubating lymphocytes with sarcoid serum or IgM purified from sarcoid serum did not stimulate T-cell proliferation. Furthermore, when Leu2+ T-cells were stimulated with irradiated allogenic B-cells, increasing concentrations of sarcoid serum had no inhibitory effects on the activation and proliferative response of the Leu2+ T-cells. Likewise, the purified IgM anti-T-cell antibodies had no inhibitory effects on the mitogenic response of Leu2+ T-cells to the anti-T-cell antigen receptor-associated T3 complex antibody OKT3. Thus, the IgM anti-T-cell autoantibodies of sarcoidosis are present at the site of disease and bind to potentially relevant T-cell subsets; however, our study found no evidence that they have an identifiable functional role in the development of the excess helper T-cell activity of sarcoidosis.