CD25 regulatory cells are involved in protection from collagen-induced arthritis in both susceptible and non-susceptible mice

CD4⁺ regulatory T cells expressing the activation marker CD25 have been strongly implicated in the control of autoimmune diseases. For example, immune compromised mice that receive splenocytes depleted of CD25⁺cells develop a variety of organ-specific autoimmune diseases such as colitis, gastritis, oophoritis, orchitis, and thyroiditis. Nonetheless, the role of regulatory T cells in many other autoimmune diseases, particularly systemic autoimmune diseases, has not been explored. We have now analyzed the role of CD25⁺CD4⁺ T cells in the control of collagen-induced arthritis (CIA), a commonly accepted model of rheumatoid arthritis. Depletion of CD25⁺ T cells in CIA susceptible DBA/1 mice leads to an earlier and more aggressive disease as evidenced by the development of severely swollen limbs following collagen injection. These mice also showed an increase in collagen specific antibodies. In addition, B6 mice, which are normally not susceptible to CIA, rapidly develop arthritis when vaccination is performed after depletion of CD25⁺ cells. Together, these findings indicate the importance of CD25⁺ cells in modulating CIA, establishing them as significant contributors in the control of chronic and systemic joint-related inflammation like that found in rheumatoid arthritis.