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

Arthritis Rheum. 1997 Aug;40(8):1493-503. doi: 10.1002/art.1780400818.

Abstract

Objective: 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-gamma, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibody Formation
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology*
  • Clone Cells / metabolism
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytotoxicity, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoblotting
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Mixed Connective Tissue Disease / immunology*
  • Peptides / immunology*
  • Phenotype
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / analysis
  • Receptors, Antigen, T-Cell / genetics
  • Ribonucleoproteins, Small Nuclear / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Autoantibodies
  • Cytokines
  • Peptides
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Ribonucleoproteins, Small Nuclear