CD25⁺ regulatory cells from HLA-DQ8 transgenic mice are capable of modulating collagen-induced arthritis

Background

In mice, CD25⁺ CD4⁺ T regulatory cells have been implicated in the control of immune responses and may have the potential to be used in therapies for autoimmune diseases, such as rheumatoid arthritis.

Objective

In order to evaluate their involvement in chronic arthritis, we depleted CD25⁺ cells in DBA/1 mice, which are susceptible to collagen-induced arthritis (CIA).

Results

Significant increases in severity and collagen-specific antibodies were seen in mice that were depleted before immunization with collagen. In vitro tests with splenocytes from depleted mice also showed increased proliferation of collagen-specific T cells, indicating that CD25⁺ regulatory cells are involved in CIA. In humans, the HLA-DQ8 molecule is strongly associated with rheumatoid arthritis. Since CD25⁺ CD4⁺ T regulatory cells are probably selected in the thymus, specific MHC class II molecules could hinder their development, which could explain the association between HLA and disease susceptibility. In order to explore this possibility, we performed similar experiments in HLA-DQ8 transgenic mice. We found that depletion of CD25⁺ cells had the same effect on CIA as seen in the DBA/1 mice. Furthermore, DQ8-restricted CD25⁺ CD4⁺ T cells were found to be as capable of suppressing the proliferation of PHA stimulated splenocytes as CD25⁺ CD4⁺ T regulatory cells isolated from DBA/1 mice.

Conclusion

These findings indicate that CD25⁺ regulatory cells can modulate arthritis and that HLA-DQ8 does not interfere in the generation of functional CD25⁺ CD4⁺ T regulatory cells.