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

Eric L. Greidinger, Tal Gazitt, Kimberly F. Jaimes, Robert W. Hoffman

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Objective. 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. Methods. 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. Results. 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)2216-2222
Number of pages7
JournalArthritis and Rheumatism
Volume50
Issue number7
DOIs
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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