Human T cell clones specific for heterogeneous nuclear ribonucleoprotein A2 autoantigen from connective tissue disease patients assist in autoantibody production.

Abstract

To identify and characterize human T cells reactive with heterogeneous nuclear RNP A2 (hnRNP A2) antigen, and to determine the ability of hnRNP-reactive T cells to assist in the production of human autoantibodies. T cells from patients with high serum levels of anti-hnRNP IgG autoantibody were stimulated with an hnRNP recombinant fusion protein, and the cells were cloned by limiting dilution. The surface phenotype and cytokine profiles of the T cells were examined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. T cell clones were cultured with highly purified autologous B cells, and the ability of T cells to enhance autoantibody production under a variety of conditions was measured by ELISA. Human T cells reactive with hnRNP antigen were cloned from 2 patients with systemic lupus erythematosus (SLE) and 1 patient with mixed connective tissue disease (MCTD). The T cells were CD4+ and had a Th1-like functional phenotype. In coculture in vitro with autologous B cells, T cell clones augmented anti-hnRNP autoantibody production and did so without the need for direct T cell-B cell contact. This study provides direct evidence for a role of anti-hnRNP-reactive T cells in autoantibody production in SLE and MCTD. These findings support the notion that hnRNP-reactive T cells play a role in the pathogenesis of these diseases.