IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow

Angela C. Quinci, Sara Vitale, Elisabetta Parretta, Alessandra Soriani, Maria L. Iannitto, Marco Cippitelli, Cinzia Fionda, Silvia Bulfone-Paus, Angela Santoni, Francesca Di Rosa

Research output: Contribution to journalArticle

Abstract

CD127 is the IL-7 receptor α-chain and its expression is tightly regulated during T-cell differentiation. We previously showed that the bone marrow (BM) is a key organ for proliferation and maintenance of both antigen-specific and CD44 high memory CD8 + T cells. Interestingly, BM memory CD8 + T cells express lower levels of membrane CD127 than do the corresponding spleen and lymph node cells. We investigated the requirements for CD127 downmodulation by CD44 high memory-phenotype CD8 + T cells in the BM of C57BL/6 mice. By comparing genetically modified (i.e. CD127tg, IL-7 KO, IL-15 KO, IL-15Rα KO) with wild-type (WT) mice, we found that the key molecule regulating CD127 downmodulation was IL-15 but not IL-7, and that the intact CD127 gene was required, including the promoter. Indeed, CD127 mRNA transcript levels were lower in CD44 high CD8 + T cells from the BM than in those from the spleen of WT mice, indicating organ-specific regulation. Although levels of the CD127 transactivator Foxo1 were low in BM CD44 high CD8 + T cells, Foxo1 was not involved in IL-15-induced CD127 downmodulation. Thus, recirculating CD44 high CD8 + T cells passing through the BM transiently downregulate CD127 in response to IL-15, with implications for human therapies acting on the IL-7/CD127 axis, for example cytokine treatments in cancer patients.

Original languageEnglish
Pages (from-to)1129-1139
Number of pages11
JournalEuropean Journal of Immunology
Volume42
Issue number5
DOIs
Publication statusPublished - May 2012

    Fingerprint

Keywords

  • γ-chain cytokines
  • T-cell homeostasis
  • T-cell memory
  • T-cell recirculation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Quinci, A. C., Vitale, S., Parretta, E., Soriani, A., Iannitto, M. L., Cippitelli, M., Fionda, C., Bulfone-Paus, S., Santoni, A., & Di Rosa, F. (2012). IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow. European Journal of Immunology, 42(5), 1129-1139. https://doi.org/10.1002/eji.201142019