title: CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10.
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.
authors.affiliation: Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Institut Pasteur, Paris, France.annacker@pasteur.fr
authors.forename: O
authors.initials: O
authors.lastname: Annacker
authors.forename: R
authors.initials: R
authors.lastname: Pimenta-Araujo
authors.forename: O
authors.initials: O
authors.lastname: Burlen-Defranoux
authors.forename: T C
authors.initials: TC
authors.lastname: Barbosa
authors.forename: A
authors.initials: A
authors.lastname: Cumano
authors.forename: A
authors.initials: A
authors.lastname: Bandeira
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D015994:Incidence; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D019282:Wasting Syndrome / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control
chemical_list: D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D017493:Leukocyte Common Antigens