IL-7 and IL-15 differentially regulate CD8+ T-cell subsets during contraction of the immune response

Blood. 2008 Nov 1;112(9):3704-12. doi: 10.1182/blood-2008-06-160945. Epub 2008 Aug 8.

Abstract

Although it is known that interleukin-7 (IL-7) and IL-15 influence the survival and turnover of CD8+ T cells, less is known about how these cytokines affect different subsets during the course of the immune response. We find that IL-7 and IL-15 differentially regulate CD8+ T-cell subsets defined by KLRG1 and CD127 expression during the contraction phase of the immune response. The provision of IL-15, or the related cytokine IL-2, during contraction led to the preferential accumulation of KLRG1(hi)CD127(lo) CD8+ T cells, whereas provision of IL-7 instead favored the accumulation of KLRG1(lo)CD127(hi) cells. While IL-7 and IL-15 both induced proliferation of KLRG1(lo) cells, KLRG1(hi) cells exhibited an extraordinarily high level of resistance to cytokine-driven proliferation in vivo despite their dramatic accumulation upon IL-15 administration. These results suggest that IL-15 and IL-2 greatly improve the survival of KLRG1(hi) CD8+ T cells, which are usually destined to perish during contraction, without inducing proliferation. As the availability of IL-15 and IL-2 is enhanced during periods of extended inflammation, our results suggest a mechanism in which a population of cytokine-dependent KLRG1(hi) CD8+ T cells is temporarily retained for improved immunity. Consideration of these findings may aid in the development of immunotherapeutic strategies against infectious disease and cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Interleukin-15 / metabolism
  • Interleukin-15 / pharmacology*
  • Interleukin-7 / metabolism
  • Interleukin-7 / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Interleukin-15 / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology

Substances

  • Interleukin-15
  • Interleukin-7
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Ovalbumin