Anti-IL-6 receptor antibody suppressed T cell activation by inhibiting IL-2 production and inducing regulatory T cells

Eur J Pharmacol. 2010 May 25;634(1-3):178-83. doi: 10.1016/j.ejphar.2010.02.026. Epub 2010 Feb 23.

Abstract

T cell activation is crucial to the pathogenesis and progression of rheumatoid arthritis. Tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 inhibitors show marked efficacy in rheumatoid arthritis patients, but their impacts on T cell activation have remained unclear. To shed light on these impacts, we examined the effects of an anti-IL-6 receptor antibody and an anti-TNFalpha antibody on T cell activation in two experimental systems: spleen cells stimulated by anti-CD3 antibody, and purified splenic CD4 T cells stimulated by both anti-CD3 and anti-CD28 antibodies. Anti-IL-6 receptor antibody significantly (but only partially) suppressed T cell activation (as indicated by [3H]-thymidine uptake and CD25 expression) and IL-2 production in both systems, and increased the frequency of regulatory T cells among spleen cells. Anti-TNFalpha antibody had no effects in either system. Neither antibody increased the expression of markers of apoptosis in CD4 T cells. In conclusion, our results show that anti-IL-6 receptor antibody significantly (but only partially) suppressed the T cell receptor signalling-induced activation of CD4 T cells and also suggest that it achieved this partial suppression by the partial inhibition of IL-2 production and the induction of regulatory T cells. In stark contrast, anti-TNFalpha antibody had no impact on T cell activation. Extrapolating these results to the clinical treatment of rheumatoid arthritis, they suggest that IL-6 blockade inhibits T cell activation, whereas TNFalpha blockade does not.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies / physiology*
  • CD4 Lymphocyte Count
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Female
  • Growth Inhibitors / physiology
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-2 / biosynthesis*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-6 / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Antibodies
  • Growth Inhibitors
  • Interleukin-2
  • Receptors, Interleukin-6