IL-15 availability conditions homeostasis of peripheral natural killer T cells

Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2663-8. doi: 10.1073/pnas.0535482100. Epub 2003 Feb 21.

Abstract

Steady-state numbers of peripheral lymphocyte are tightly controlled. For conventional T cells, signals delivered through the interaction of the T cell receptor (TCR) with antigen-loaded MHC molecules are required for the peripheral survival of naive T cells and for their homeostatic expansion in lymphopenic hosts. Cytokines, including IL-7, are also essential for survival of peripheral naive T cells. CD1d-restricted, V alpha 14(+) natural killer (NK)-T cells are a specialized autoreactive T subset with immunoregulatory activity. The relative roles of TCR engagement and cytokine signaling in the peripheral homeostasis of V alpha 14(+) NK-T cells were investigated. After adoptive transfer, the survival and expansion of peripheral V alpha 14(+) NK-T cells was independent of CD1d expression in the host. In contrast, IL-15 (but not IL-7) was required for maintenance of peripheral CD1d-reactive V alpha 14(+) T cells. Comparison of V alpha 14(+) T cell transfers into NK-proficient vs. deficient hosts suggests that NK-T cells and NK cells compete for peripheral resources. Our results indicate that IL-15 maintains the homeostasis of peripheral V alpha 14(+) NK-T cells. In contrast, TCR "tickling" of NK-T cells, if it occurs under steady-state conditions, does not by itself provide a sufficient signal for their peripheral survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD1 / metabolism
  • Antigens, CD1d
  • Bromodeoxyuridine / pharmacology
  • Cell Division
  • Cell Survival
  • Flow Cytometry
  • Interleukin-15 / biosynthesis*
  • Interleukin-15 / metabolism
  • Interleukin-7 / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / physiology*
  • Liver / immunology
  • Liver / metabolism
  • Lymph Nodes / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Signal Transduction
  • Spleen / cytology
  • Thymus Gland / cytology
  • Time Factors

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • Interleukin-15
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Bromodeoxyuridine