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


CONCLUSIONS
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.
Greidinger
Eric L
EL
University of Miami, and the Veterans Affairs Medical Center, Miami, Florida, USA.
Gazitt
Tal
T
Jaimes
Kimberly F
KF
Hoffman
Robert W
RW
D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000032:analysis*; D001782:Blood Donors; D016022:Case-Control Studies; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003240:Connective Tissue Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D055517:snRNP Core Proteins