A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses

Eur J Immunol. 2002 Aug;32(8):2124-32. doi: 10.1002/1521-4141(200208)32:8<2124::AID-IMMU2124>3.0.CO;2-S.


The chemokine receptors CCR5 and CXCR3 have been implicated as playing a central role in directing a Th1 inflammatory response. Here, we investigated whether a synthetic CCR5 antagonist affects the process of T cell migration to sites of inflammation. Immunization of DBA/1 mice with type II collagen resulted in typical arthritis, which is associated with cellular infiltration. Treatment with a CCR5 antagonist strikingly affected the development of arthritis by reducing both incidence and severity of disease. There was no substantial difference between collagen-immunized mice with and without antagonist treatment in the induction of anti-collagen T cell responses and the capacity to produce IL-12. This endogenous IL-12 functioned to induce comparable levels of CCR5 in these two immunized groups of T cells. Whereas a massive infiltration of inflammatory cells including CCR5(+) T cells occurred in the joints of mice immunized without antagonist, cellular infiltration in the antagonist-treated group was only marginal. These results indicate that administration of a CCR5 antagonist inhibits the development of arthritis not by affecting the generation of collagen-sensitized T cells but by interfering with their migration to joint lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use*
  • Animals
  • Antibody Formation
  • Arthritis / prevention & control*
  • CCR5 Receptor Antagonists*
  • Cell Movement / drug effects
  • Collagen / immunology*
  • Interleukin-12 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred DBA
  • Quaternary Ammonium Compounds / therapeutic use*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology


  • Amides
  • CCR5 Receptor Antagonists
  • Quaternary Ammonium Compounds
  • Interleukin-12
  • Collagen
  • TAK 779