Spatial distribution, kinetics, signaling and cytokine production during homeostasis driven proliferation of CD4+ T cells

Mol Immunol. 2009 Jul;46(11-12):2403-12. doi: 10.1016/j.molimm.2009.04.019. Epub 2009 May 17.

Abstract

During recovery from lymphopenia, the naïve T-cells undergo homeostasis driven proliferation (HDP) and acquire a memory phenotype. The HDP of T-cells requires signals derived from T-cell-receptor, p56lck kinase, IL-7R and IL-15R. However, the role of other signaling molecules during HDP of CD4+ T-cells remains speculative. The differentiation of naïve T-cells into Th1/Th2/Th17 or Treg populations during HDP is not well understood. Present report describes the spatial and signaling characteristics of HDP of CD4+ T-cells and their cytokine profiles. The HDP of CD4+ T-cells was found to occur only in specific areas (T-cell zones) of secondary lymphoid organs of lymphopenic mice. The inhibitors of MEK and PKC and their combination with inhibitors of PI3kinase and mTOR suppressed mitogen induced T-cell proliferation without affecting their HDP. The CD4+ T-cells taken from reconstituted lymphopenic mice showed activation of proteins involved in NF-kappaB pathway, significantly higher production of pro-inflammatory cytokine IL-6, and lower production of IL-4 as compared to T-cells from normal mice. Plumbagin, a known NF-kappaB blocker inhibited survival as well as HDP of CD4+ T-cells and IL-6 production in activated T-cells. Our results demonstrate the essential role of NF-kappaB during HDP of T-cells.

MeSH terms

  • Animals
  • Ascitic Fluid / immunology
  • Ascitic Fluid / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Proliferation*
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Homeostasis / immunology*
  • Immunologic Memory
  • Kinetics
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Naphthoquinones / pharmacology
  • Peritoneal Cavity / pathology
  • Protein Kinase C / metabolism
  • Signal Transduction
  • Spleen / immunology
  • Spleen / pathology

Substances

  • Cytokines
  • NF-kappa B
  • Naphthoquinones
  • Protein Kinase C
  • MAP Kinase Kinase Kinases
  • plumbagin