Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms

J Immunol. 2005 May 15;174(10):6039-44. doi: 10.4049/jimmunol.174.10.6039.

Abstract

Transfer of naive CD4 T cells into lymphopenic mice initiates a proliferative response of the transferred cells, often referred to as homeostatic proliferation. Careful analysis reveals that some of the transferred cells proliferate rapidly and undergo robust differentiation to memory cells, a process we have designated spontaneous proliferation, and other cells proliferate relatively slowly and show more limited evidence of differentiation. In this study we report that spontaneous proliferation is IL-7 independent, whereas the slow proliferation (referred to as homeostatic proliferation) is IL-7 dependent. Administration of IL-7 induces homeostatic proliferation of naive CD4 T cells even within wild-type recipients. Moreover, the activation/differentiation pattern of the two responses are clearly distinguishable, indicating that different activation mechanisms may be involved. Our results reveal the complexity and heterogeneity of lymphopenia-driven T cell proliferation and suggest that they may have fundamentally distinct roles in the maintenance of CD4 T cell homeostasis.

Publication types

  • Comparative Study

MeSH terms

  • Adoptive Transfer* / methods
  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cell Proliferation*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Infusion Pumps, Implantable
  • Interleukin-7 / administration & dosage
  • Interleukin-7 / physiology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Proteins / administration & dosage

Substances

  • DNA-Binding Proteins
  • Interleukin-7
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • V(D)J recombination activating protein 2