Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7.
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.
Peffault de Latour
Régis
R
Unité INSERM U 668, Unité du Développement des Lymphocytes, Institut Pasteur, Paris, France.
Dujardin
Hélène C
HC
Mishellany
Florence
F
Burlen-Defranoux
Odile
O
Zuber
Julien
J
Marques
Rute
R
Di Santo
James
J
Cumano
Ana
A
Vieira
Paulo
P
Bandeira
Antonio
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation; D015851:Interleukin-7 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000502:physiology*; D013950:Thymus Gland / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015851:Interleukin-7; D015375:Receptors, Interleukin-2