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Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells

Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells

Authors :
Charles S. Carter
Hua Zhang
Margaret V. Brown
Brenna J. Hill
Daniel C. Douek
Thomas A. Fleisher
Lauren M. Long
Jay A. Berzofsky
Martin Guimond
Donna Bernstein
Elizabeth J. Read
Kevin S. Chua
Veena Kapoor
Crystal L. Mackall
Lee J. Helman
Source :
Nature Medicine. 11:1238-1243
Publication Year :
2005
Publisher :
Springer Science and Business Media LLC, 2005.

Abstract

CD4(+)CD25(+) regulatory T (T(reg)) cells have a crucial role in maintaining immune tolerance. Mice and humans born lacking T(reg) cells develop severe autoimmune disease, and depletion of T(reg) cells in lymphopenic mice induces autoimmunity. Interleukin (IL)-2 signaling is required for thymic development, peripheral expansion and suppressive activity of T(reg) cells. Animals lacking IL-2 die of autoimmunity, which is prevented by administration of IL-2-responsive T(reg) cells. In light of the emerging evidence that one of the primary physiologic roles of IL-2 is to generate and maintain T(reg) cells, the question arises as to the effects of IL-2 therapy on them. We monitored T(reg) cells during immune reconstitution in individuals with cancer who did or did not receive IL-2 therapy. CD4(+)CD25(hi) cells underwent homeostatic peripheral expansion during immune reconstitution, and in lymphopenic individuals receiving IL-2, the T(reg) cell compartment was markedly increased. Mouse studies showed that IL-2 therapy induced expansion of existent T(reg) cells in normal hosts, and IL-2-induced T(reg) cell expansion was further augmented by lymphopenia. On a per-cell basis, T(reg) cells generated by IL-2 therapy expressed similar levels of FOXP3 and had similar potency for suppression compared to T(reg) cells present in normal hosts. These studies suggest that IL-2 and lymphopenia are primary modulators of CD4(+)CD25(+) T(reg) cell homeostasis.

Details

ISSN :
1546170X and 10788956
Volume :
11
Database :
OpenAIRE
Journal :
Nature Medicine
Accession number :
edsair.doi.dedup.....e0787a5bee1533246b56a9c2650ea983
Full Text :
https://doi.org/10.1038/nm1312