We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Lymphopenia and interleukin-2 therapy alter homeostasis of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells.
- Authors
Hua Zhang; Chua, Kevin S.; Guimond, Martin; Kapoor, Veena; Brown, Margaret V.; Fleisher, Thomas A.; Long, Lauren M.; Bernstein, Donna; Hill, Brenna J.; Douek, Daniel C.; Berzofsky, Jay A.; Carter, Charles S.; Read, E. J.; Helman, Lee J.; Mackall, Crystal L.
- Abstract
CD4+CD25+ regulatory T (Treg) cells have a crucial role in maintaining immune tolerance. Mice and humans born lacking Treg cells develop severe autoimmune disease, and depletion of Treg cells in lymphopenic mice induces autoimmunity. Interleukin (IL)-2 signaling is required for thymic development, peripheral expansion and suppressive activity of Treg cells. Animals lacking IL-2 die of autoimmunity, which is prevented by administration of IL-2–responsive Treg cells. In light of the emerging evidence that one of the primary physiologic roles of IL-2 is to generate and maintain Treg cells, the question arises as to the effects of IL-2 therapy on them. We monitored Treg cells during immune reconstitution in individuals with cancer who did or did not receive IL-2 therapy. CD4+CD25hi cells underwent homeostatic peripheral expansion during immune reconstitution, and in lymphopenic individuals receiving IL-2, the Treg cell compartment was markedly increased. Mouse studies showed that IL-2 therapy induced expansion of existent Treg cells in normal hosts, and IL-2–induced Treg cell expansion was further augmented by lymphopenia. On a per-cell basis, Treg cells generated by IL-2 therapy expressed similar levels of FOXP3 and had similar potency for suppression compared to Treg cells present in normal hosts. These studies suggest that IL-2 and lymphopenia are primary modulators of CD4+CD25+ Treg cell homeostasis.
- Subjects
INTERLEUKIN-2; HOMEOSTASIS; T cells; IMMUNOLOGICAL tolerance; AUTOIMMUNE diseases
- Publication
Nature Medicine, 2005, Vol 11, Issue 11, p1238
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1312