Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7 |
| |
Authors: | Peffault de Latour Régis Dujardin Hélène C Mishellany Florence Burlen-Defranoux Odile Zuber Julien Marques Rute Di Santo James Cumano Ana Vieira Paulo Bandeira Antonio |
| |
Institution: | Unité INSERM U 668, Unité du Développement des Lymphocytes, Institut Pasteur, Paris, France. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《Blood》浏览原始摘要信息 |
| 点击此处可从《Blood》下载免费的PDF全文 |
|