ANALYSIS OF HUMAN T-CELL AND B-CELL RESPONSES AGAINST U-SMALL NUCLEARRIBONUCLEOPROTEIN 70-KD, B-POLYPEPTIDES, AND D-POLYPEPTIDES AMONG PATIENTS WITH SYSTEMIC-LUPUS-ERYTHEMATOSUS AND MIXED CONNECTIVE-TISSUE-DISEASE

Objective. To analyze T and B cell reactivity with U small nuclear RNP (snRNP) 70-kd, B, and D polypeptides among patients with connective t issue disease (CTD) and to examine the functional characteristics of s nRNP-reactive T cell clones. Methods. We used an snRNP enzyme-linked i mmunosorbent assay and immunoblotting to characterize antibodies in pa tients' 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 cytoki ne profiles of T cell clones. Results. Patients showed T cell responsi veness to snRNP polypeptides that paralleled their autoantibody reacti vities. A total of 256 clones were generated, and clones were identifi ed which were specific for the 70-kd, B, or D polypeptides. Clones exp ressed a T helper cell phenotype, and were found to produce substantia l quantities of both interleukin-4 (IL-4) and interferon-gamma, and le sser quantities of IL-2 and IL-6, Conclusion. These results show that CTD patients have clonable circulating snRNP-reactive T cells that par allel the specificity of snRNP-reactive antibodies in their sera, The snRNP-reactive T cells exhibit a helper cell phenotype and produce cyt okines which are important in B cell help and differentiation.