Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers.
We show that the lymphoid hyperplasia observed in IL-2Ralpha- and IL-2-deficient mice is due to the lack of a population of regulatory cells essential for CD4 T cell homeostasis. In chimeras reconstituted with bone marrow cells from IL-2Ralpha-deficient donors, restitution of a population of CD25(+)CD4(+) T cells prevents the chaotic accumulation of lymphoid cells, and rescues the mice from autoimmune disease and death. The reintroduction of IL-2-producing cells in IL-2-deficient chimeras establishes a population of CD25(+)CD4(+) T cells, and restores the peripheral lymphoid compartments to normal. The CD25(+)CD4(+) T cells regulated selectively the number of naive CD4(+) T cells transferred into T cell-deficient hosts. The CD25(+)CD4(+)/naive CD4 T cell ratio and the sequence of cell transfer determines the homeostatic plateau of CD4(+) T cells. Overall, our findings demonstrate that IL-2Ralpha is an absolute requirement for the development of the regulatory CD25(+)CD4(+) T cells that control peripheral CD4 T cell homeostasis, while IL-2 is required for establishing a sizeable population of these cells in the peripheral pools.
Almeida
Afonso R M
AR
Lymphocyte Population Biology, Unité de Recherche Associée Centre National de la Recherche Scientifique 1961, Institut Pasteur, Paris, France.
Legrand
Nicolas
N
Papiernik
Martine
M
Freitas
António A
AA
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015375:Receptors, Interleukin-2