Expression of 3G11 epitope defines subpopulations of regulatory T cells with different suppressive potency

3G11, a sialylated carbohydrate epitope on the disialoganglioside molecule, is expressed predominantly on the surface of mouse CD4(+) T cells. Our previous studies suggested that lack of the 3G11 molecule could be a new cell surface marker for regulatory CD4(+) T cells. In the present study, we explore the relationship between 3G11(-) and CD25(+) T cells, a well-defined, naturally occurring regulatory T cell population. We found that a large proportion of CD25(+)CD4(+) T cells lack expression of 3G11 and that more 3G11(-)CD4(+) T cells express Foxp3 compared to the 3G11(+)CD4(+) population. Based on 3G11 and CD25 expression we sorted four CD4(+) T cell subpopulations and tested their phenotypes. Among four CD25/3G11-related CD4(+) T cell subpopulations, CD25(+)3G11(-) T cells expressed the highest levels of Foxp3 and IL-10 and most efficiently inhibited mitogenic and antigen-specific immune responses in vitro and clinical EAE in vivo, while CD25(-)3G11(+) T cells produced a higher level of proinflammatory cytokines and enhanced autoimmune responses. Thus, among CD4(+)CD25(+) T cells, CD25(+)3G11(-) T cells represent a more effective Treg subpopulation than CD25(+)3G11(+) T cells.