The role CD4+ CD25+ regulatory T cells (Treg) play in modulating the immune response has been investigated extensively over recent years. Much of the work to date has used the activation marker CD25 to define, enrich and deplete Treg. However, the identification of FoxP3 as a definitive marker of Treg has allowed us to study the effect of monoclonal antibodies against CD25 on regulatory T‐cell populations. Recently, published data have indicated that Treg are inactivated, not depleted, through treatment with anti‐CD25 monoclonal antibody. Using FoxP3‐Green fluorescent protein reporter mice, we show that treatment with the CD25 MoAb PC61 depleted a subpop ulation of Treg. The depleted Treg population expressed low levels of the CD69 marker, indicating an inactive phenotype. In addition, PC61 treatment altered the function of the remaining regulatory T‐cell population, preventing their ability to modulate autoimmune diseases. Thus, our results have important implications with regard to interpreting experimental outcomes from in vivo anti‐CD25 treatments.

Summary IL-12p40 and macrophages are essential for the induction of disease in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis. In this paper, we show that treatment of mice with opsonized erythrocytes, which have been shown to ligate Fcg receptors on macrophages and alter their cytokine profile, significantly delayed the onset of experimental autoimmune encephalomyelitis. This protection correlated to the induction of Th2 responses by autoreactive T cells, enhanced basal systemic responses and a significant downregulation of IL12p40 and nitric oxide synthase-2, but not IFN-g expression. IL-4 was essential for the protection by opsonized erythrocytes as the effects of treatment were eliminated in IL-4-deficient mice. Together these studies suggest that the ligation of Fcg receptors can modify the development of autoimmune disease by altering macrophage activation and enhancing Th2 responses.

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