Abstract
Mice lacking interleukin-7 (IL-7–/– mice) have no signs of autoimmune disease, contrary to other models of lymphopenia. We investigated whether the absence of disease was due to the fact that IL-7 is dispensable for the ontogeny, function, and homeostasis of regulatory CD4+ T cells. We show here that the establishment of the peripheral pool of Foxp3-expressing regulatory cells is IL-7 independent, and the premature involution of the thymus in IL-7–/– mice does not change the representation of the CD4+CD25+ T-cell compartment. In addition, CD4+CD25+ T cells expand in the absence of IL-7, without losing Foxp3 expression. The frequency of activated peripheral CD4+ T cells increases with age in both the CD25– and CD25+ compartments, with the CD4+CD25+ T cells displaying signs of constant activation. IL-7–/– CD4+CD25+ T cells control inflammatory bowel disease induced by IL-7–/– T cells even in hosts lacking IL-7. Depletion of the CD25+ T-cell subset after thymic involution results in a mild form of inflammatory bowel disease (IBD), which resolves concomitantly with the regeneration of this subset. This study shows for the first time that IL-7–/– mice have a robust regulatory Foxp3-expressing CD4+ T-cell compartment that controls T-cell–mediated disease. It also highlights the potential of the regulatory Foxp3-expressing CD4+CD25– T-cell population to restore a functional CD4+CD25+ T-cell compartment through an IL-7–independent pathway.
Pathophysiological significance of the two-pore domain K+ channel K2P5.1 in splenic CD4+CD25− T cell subset from a chemically-induced murine inflammatory bowel disease model
