Analysis of human t cell and b cell responses against u small nuclear ribonucleoprotein 70‐kd, b, and d polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease

AbstractObjective. To analyze T and B cell reactivity with U small nuclear RNP (snRNP) 70‐kd, B, and D polypeptides among patients with connective tissue disease (CTD) and to examine the functional characteristics of snRNP‐reactive T cell clones.Methods. We used an snRNP enzyme‐linked immunosorbent assay and immunoblotting to characterize antibodies in patients' sera. We used human recombinant fusion proteins 70 kd, B, and D to stimulate and clone snRNP‐reactive T cells from CTD patients. We analyzed the cell surface phenotype, antigenic specificity, and cytokine profiles of T cell clones.Results. Patients showed T cell responsiveness to snRNP polypeptides that paralleled their autoantibody reactivities. A total of 256 clones were generated, and clones were identified which were specific for the 70‐kd, B, or D polypeptides. Clones expressed a T helper cell phenotype, and were found to produce substantial quantities of both interleukin‐4 (IL‐4) and interferon‐γ, and lesser quantities of IL‐2 and IL‐6.Conclusion. These results show that CTD patients have clonable circulating snRNP‐reactive T cells that parallel the specificity of snRNP‐reactive antibodies in their sera. The snRNP‐reactive T cells exhibit a helper cell phenotype and produce cytokines which are important in B cell help and differentiation.