Patients with relapsing-remitting multiple sclerosis have normal Treg function when cells expressing IL-7 receptor alpha-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+CD25high 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 alpha-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+CD25high T cells isolated from MS patients. However, when CD127(high) cells were removed from the CD4+CD25high population, 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 CD127high cells, CD4+CD25high T cells from patients with MS and healthy individuals had similar regulatory function. Additional analysis indicated that the CD127high cells within the CD4+CD25high 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+CD25highCD127low Tregs from MS patients and healthy individuals exhibit similar suppressive functions. The decreased inhibitory function of unfractioned CD4+CD25high cells previously observed might be due to abnormal activation of CD127high T cells in patients with MS.
Michel
Laure
L
INSERM U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation (ITERT), and Faculté de Médecine, Université de Nantes, Nantes, France.
Berthelot
Laureline
L
Pettré
Ségolène
S
Wiertlewski
Sandrine
S
Lefrère
Fabienne
F
Braudeau
Cécile
C
Brouard
Sophie
S
Soulillou
Jean-Paul
JP
Laplaud
David-Axel
DA