AUTOANTIBODIES TO ACTIVATED LYMPHOCYTES IN SLE

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This laboratory has had a long-term interest in study of the nature and significance of anti-lymphocyte autoantibodies in systemic lupus erythematosus (SLE). Very recent investigations utilizing a reverse hemolytic plaque technique have demonstrated increased numbers of endogenously activated T cells (T-PFC), which shed soluble membrane products, in the circulation of patients with active SLE. These T-PFC are strongly correlated with the presence of activated B cells spontaneously secreting immunoglobulin. This suggests that such activated T cells may reflect important immunoregulatory mechanisms. Other data indicate that relatively warm-reactive antibodies of the IgG class exhibit unusual reactivity both with activated T cells and with their soluble products. The over-all objective of this proposal is to further characterize the nature of activated lymphocytes and specifically-reactive antibodies in SLE, and to define their role in the natural history of this disorder. Serial observations in individual patients will provide information concerning the relationship of T-PFC with other immunologic abnormalities and disease expression. SLE antibodies and monoclonal antibodies to resting lumphocytes and to activation neoantigens will be used as probes to identify both the types of T cells which are spontaneously activated and the molecules which are expressed or shed from their surface membranes. The relationship of cell surface neoantigen expression with other nuclear and membrane parameters of cell activation will be examined by flow cytometry. Immune complexes of soluble products of activated T cells and autoantibody will be sought in serum and serum cryoprecipitates. Hybridoma antibodies specific for activated lymphocyte antigens and SLE lymphocyte antigens will be produced.