Human double-negative T cells in systemic lupus erythematosusprovide help for IgG and are restricted by CD1c

P. A. Sieling, S. A. Porcelli, B. T. Duong, F. Spada, B. R. Bloom, B. Diamond, B. H. Hahn

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

To understand the mechanism of T cell help for IgG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because 1) DN T cells are present at unusually high frequency in patients with SLE and can induce pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1+ APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-γ, whereas DN T cells from healthy donors produced IFN-γ, but no IL-4. In general, cells from patients with highly active disease produced high levels of IFN-γ; cells from those with little activity produced high IL-4. Coculture of CD1c-directly reactive T cells from healthy donors with CD1c+ B cells elicited IgM Abs, but little or no IgG. In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c+ B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of DN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c+ B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.

Original languageEnglish (US)
Pages (from-to)5338-5344
Number of pages7
JournalJournal of Immunology
Volume165
Issue number9
DOIs
StatePublished - Nov 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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