A novel population of B7-1+ T cells producing intracellular IL-4 is decreased in patients with multiple sclerosis

Eur J Immunol. 2000 Jul;30(7):2092-100. doi: 10.1002/1521-4141(200007)30:7<2092::AID-IMMU2092>3.0.CO;2-7.

Abstract

We identified a novel population of human T cells, studied directly ex vivo, that co-express surface B7-1 and intracellular IL-4. These peripheral blood B7-1+/CD4+ T cells expressed cell surface molecules associated with differentiation including CD45RO and MHC class II, yet were CD69(-) and CD25(-). In short-term cultures, T cell receptor (TCR) cross-linking induced further IL-4 production with little IFN-gamma or TNF-alpha. In marked contrast, CD4+ T cells negative for B7-1 expressed intracellular IFN-gamma and high amounts of TNF-alpha but little IL-4 upon TCR cross-linking. The CD4+/B7-1+/IL-4-expressing T cells were of polyclonal origin based on their diverse TCR repertoire. To explore the biological significance of this B7-1+/IL-4+ T cell population and to assess its potential regulatory role in autoimmune disease, we examined whether these T cells isolated ex vivo were altered in subjects with multiple sclerosis (MS). While the frequency of B7-1+ T cells was enhanced in patients with MS as compared to normal subjects, there was a significant diminution of B7-1+/IL-4+ T cells in the patients. The decrease in these IL-4-producing T cells in patients with autoimmune disease is consistent with a possible role as immunoregulatory T cells.

Publication types

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

MeSH terms

  • Antigens, CD / biosynthesis
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / immunology*
  • B7-2 Antigen
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis*
  • Intracellular Fluid / immunology
  • Leukocytes, Mononuclear / immunology
  • Membrane Glycoproteins / biosynthesis
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma