Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-γ
| Autor: | Kelchtermans, Hilde, De Klerck, Bert, Mitera, Tania, Van Balen, Maarten, Bullens, Dominique, Billiau, Alfons, Leclercq, Georges, Matthys, Patrick |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Freund's Adjuvant Antigen-Presenting Cells chemical and pharmacologic phenomena Lymphocyte Activation T-Lymphocytes Regulatory regulatory T cells Lymphocyte Depletion Immunophenotyping Interferon-gamma Mice Transforming Growth Factor beta interferon-γ Animals Collagen Type II Receptors Interferon Mice Knockout Reverse Transcriptase Polymerase Chain Reaction autoimmunity Antibodies Monoclonal hemic and immune systems Receptors Interleukin-2 Arthritis Experimental Coculture Techniques arthritis Mice Inbred DBA Female Immunization Research Article |
| Zdroj: | Arthritis Research & Therapy |
| ISSN: | 1478-6362 1478-6354 |
| Popis: | Mice with a deficiency in IFN-gamma or IFN-gamma receptor (IFN-gammaR) are more susceptible to collagen-induced arthritis (CIA), an experimental autoimmune disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility of IFN-gammaR knock-out (KO) mice is associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II (CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role of Treg cells in the effector phase of CIA. IFN-gammaR deficiency did not affect the number of CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition, CD4+CD25+ T cells isolated from naive IFN-gammaR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more impaired in IFN-gammaR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly specific marker for Treg cells, was lower. We further demonstrated that the effect of endogenous IFN-gamma, which accounts for more suppressive activity in wild-type mice, concerns both Treg cells and accessory cells. Our results demonstrate that the decrease in Treg cell activity in CIA is counter-regulated by endogenous IFN-gamma. |
| Databáze: | OpenAIRE |
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