Prolonged exposure of naïve CD8+ T cells to interleukin-7 or interleukin-15 stimulates proliferation without differentiation or loss of telomere length

Immunology. 2006 Oct;119(2):243-53. doi: 10.1111/j.1365-2567.2006.02429.x.

Abstract

Interleukin (IL)-7 and IL-15 are cytokines implicated in homeostatic control of the peripheral CD8 T-cell pool. We compared the effects of IL-7 and IL-15 on survival and proliferation of purified human CD8+ T-cell subsets. Low concentrations of either cytokine reduced the spontaneous apoptosis of all subsets, and enhancement of survival corresponded to the extent of Bcl-2 up-regulation. Surprisingly, although minimal proliferation of naïve CD8+ T cells was observed during the first week of culture with cytokines, a marked expansion of these cells occurred at later time points, particularly in response to IL-15. This occurred largely without phenotypic change or acquisition of effector function, indicating a dissociation of differentiation from proliferation. Notably, progression of naïve CD8+ T cells through several cell divisions resulted in up-regulation of telomerase and the maintenance of telomere length. These data show that IL-7 and IL-15 induce cell proliferation and rescue from apoptosis in a concentration, time and subset-dependent manner, and have implications for the homeostatic expansion of the naïve CD8+ T-cell pool.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Dose-Response Relationship, Immunologic
  • Flow Cytometry / methods
  • Humans
  • Immunophenotyping
  • Interleukin-15 / immunology*
  • Interleukin-7 / immunology*
  • Leukocyte Common Antigens / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, CCR7
  • Receptors, Chemokine / metabolism
  • T-Lymphocyte Subsets / immunology
  • Telomerase / metabolism
  • Telomere / immunology*

Substances

  • CCR7 protein, human
  • Interleukin-15
  • Interleukin-7
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, CCR7
  • Receptors, Chemokine
  • Telomerase
  • Leukocyte Common Antigens