Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2124-2132 |
Number of pages | 9 |
Journal | European Journal of Immunology |
Volume | 32 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2002 |
Externally published | Yes |
Keywords
- Chemokine
- Chemokine receptor
- IL-12
- Rheumatoid arthritis
- T cell migration
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology