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The Journal of Immunology, 2001, 166: 3008-3018.
Copyright © 2001 by The American Association of Immunologists

CD25+ CD4+ T Cells Regulate the Expansion of Peripheral CD4 T Cells Through the Production of IL-101

Oliver Annacker2, Ricardo Pimenta-Araujo, Odile Burlen-Defranoux, Theolis C. Barbosa3, Ana Cumano and Antonio Bandeira

Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Institut Pasteur, Paris, France

The mechanisms by which the immune system achieves constant T cell numbers throughout life, thereby controlling autoaggressive cell expansions, are to date not completely understood. Here, we show that the CD25+ subpopulation of naturally activated (CD45RBlow) CD4 T cells, but not CD25- CD45RBlow CD4 T cells, inhibits the accumulation of cotransferred CD45RBhigh CD4 T cells in lymphocyte-deficient mice. However, both CD25+ and CD25- CD45RBlow CD4 T cell subpopulations contain regulatory cells, since they can prevent naive CD4 T cell-induced wasting disease. In the absence of a correlation between disease and the number of recovered CD4+ cells, we conclude that expansion control and disease prevention are largely independent processes. CD25+ CD45RBlow CD4 T cells from IL-10-deficient mice do not protect from disease. They accumulate to a higher cell number and cannot prevent the expansion of CD45RBhigh CD4 T cells upon transfer compared with their wild-type counterparts. Although CD25+ CD45RBlow CD4 T cells are capable of expanding when transferred in vivo, they reach a homeostatic equilibrium at lower cell numbers than CD25- CD45RBlow or CD45RBhigh CD4 T cells. We conclude that CD25+ CD45RBlow CD4 T cells from nonmanipulated mice control the number of peripheral CD4 T cells through a mechanism involving the production of IL-10 by regulatory T cells.




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