Patients with relapsing-remitting multiple sclerosis have normal Treg function when cells expressing IL-7 receptor α-chain are excluded from the analysis

Multiple sclerosis (MS) is a chronic inflammatory disease that results in demyelination in the central nervous system, and a defect in the regulatory function of CD4(+)CD25(high) T cells has been implicated in the pathogenesis of the disease. Here, we reanalyzed the function of this T cell subset in patients with MS, but we depleted cells expressing IL-7 receptor cc-chain (CD127), a marker recently described as present on activated T cells but not Tregs. Similar to other studies, we observed a marked defect in the suppressive function of unseparated CD4(+)CD25(high) T cells isolated from MS patients. However, when CD127(high) cells were removed from the CD4(+)CD25(high p)opulation, patient and control cells inhibited T cell proliferation and cytokine production equally. Likewise, when the CD25 gate used to sort the cells was stringent enough to eliminate CD127(high) cells, CD4(+)CD25(high) T cells from patients with MS and healthy individuals had similar regulatory function. Additional analysis indicated that the CD127(high) cells within the CD4(+)CD25(high) T cell population from patients with MS appeared more proliferative and secreted more IFN-gamma and IL-2 than the same cells from healthy individuals. Taken together, we conclude that CD4(+)CD25(high) CD127(low) Tregs from MS patients and healthy individuals exhibit similar suppressive functions. The decreased inhibitory function of unfractioned CD4(+)CD25(high) cells previously observed might be due to abnormal activation of CD127(high) T cells in patients with MS.