Non-redundant role for IL-7R signaling for the survival of CD8+ memory T cells

Roberto Carrio, Cleo E. Rolle, Thomas R. Malek

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

IL-7 and IL-15 are important cytokines for CD8 memory T cells. However, the extent that IL-7 is essential for CD8 T cell memory remains unclear because blocking IL-7 in vivo results in near complete inhibition of T cell development with the few mature T cells exhibiting functional abnormalities. To bypass this complication, CD8 memory development was examined utilizing a mouse model where transgenic IL-7Rα was selectively expressed in the thymus of IL-7Rα-/- mice. T cell development was corrected but the resulting peripheral T cells were essentially IL-7 non-responsive. Activation of IL-7R-defective OT-I CD8+ T cells with OVA257-264 and IL-2 readily yielded CTL. Upon further culture with IL-15, these CTL expressed phenotypic and functional properties of central memory-like cells. Thus, IL-7R-defective CD8+ T cells do not exhibit intrinsic defects in effector or memory development. When IL-7R-defective OT-I CTL were adoptively transferred into normal or EL-15-/- recipient mice in a non-inflammatory setting, they converted into memory-like cells, but did not persist, which was even more striking in IL-15-/- recipients. This poor persistence was rescued after expression of transgenic Bcl-2 in IL-7R-defective OT-I T cells. Collectively, these data indicate that IL-7 is non-redundantly required for the survival of CD8 memory T cells.

Original languageEnglish (US)
Pages (from-to)3078-3088
Number of pages11
JournalEuropean Journal of Immunology
Volume37
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • Bcl-2
  • CD8 T memory
  • CTL
  • IL-15
  • IL-7

ASJC Scopus subject areas

  • Immunology

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