CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10

O Annacker, R Pimenta-Araujo… - The Journal of …, 2001 - journals.aai.org
O Annacker, R Pimenta-Araujo, O Burlen-Defranoux, TC Barbosa, A Cumano, A Bandeira
The Journal of Immunology, 2001journals.aai.org
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 (CD45RB
low) CD4 T cells, but not CD25− CD45RB low CD4 T cells, inhibits the accumulation of
cotransferred CD45RB high CD4 T cells in lymphocyte-deficient mice. However, both
CD25+ and CD25− CD45RB low CD4 T cell subpopulations contain regulatory cells, since …
Abstract
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 (CD45RB low) CD4 T cells, but not CD25− CD45RB low CD4 T cells, inhibits the accumulation of cotransferred CD45RB high CD4 T cells in lymphocyte-deficient mice. However, both CD25+ and CD25− CD45RB low 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+ CD45RB low 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 CD45RB high CD4 T cells upon transfer compared with their wild-type counterparts. Although CD25+ CD45RB low CD4 T cells are capable of expanding when transferred in vivo, they reach a homeostatic equilibrium at lower cell numbers than CD25− CD45RB low or CD45RB high CD4 T cells. We conclude that CD25+ CD45RB low 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.
journals.aai.org