Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers

J Immunol. 2002 Nov 1;169(9):4850-60. doi: 10.4049/jimmunol.169.9.4850.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Animals
  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / transplantation
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Interphase / genetics
  • Interphase / immunology
  • Lymphocyte Count
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Lymphopenia / mortality
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Radiation Chimera / genetics
  • Radiation Chimera / immunology
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / physiology*
  • Survival Analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation

Substances

  • Adjuvants, Immunologic
  • Interleukin-2
  • Receptors, Interleukin-2