Interleukin-15 selectively expands CD57+ CD28- CD4+ T cells, which are increased in active rheumatoid arthritis

Clin Immunol. 2007 Sep;124(3):328-35. doi: 10.1016/j.clim.2007.06.001. Epub 2007 Jul 23.

Abstract

Proinflammatory cytokines as well as CD4(+) T cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recently, an increase of CD57(+) or CD28(-)CD4(+) T cells was demonstrated in RA, although the mechanism of the increase of these T cells is unclear. In this study, we first examined the relationship between CD57(+)CD4(+) T cells and CD28(-)CD4(+) T cells and found CD57(+)CD28(-)CD4(+) T cells, but neither CD57(+)CD28(+) nor CD57(-)CD28(+) cells, expanded in the peripheral blood of active RA. In vitro experiments revealed that CD57(+)CD28(-)CD4(+) T cells selectively expanded in response to IL-15. Furthermore IL-15-stimulated CD57(+)CD28(-)CD4(+) T cells induced TNF-alpha production from monocytes. These results suggest that CD57(+)CD28(-)CD4(+) T cells are involved in the pathogenesis of RA by responding to IL-15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology*
  • CD28 Antigens*
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD57 Antigens / biosynthesis*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-15 / metabolism*
  • Interleukin-15 / pharmacology
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CD28 Antigens
  • CD57 Antigens
  • Interleukin-15
  • Tumor Necrosis Factor-alpha