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

18 Citations (Scopus)

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

Interleukin-15
Bone Marrow
T-Lymphocytes
Phenotype
Interleukin-7
Spleen
Interleukin-7 Receptors
CD44 Antigens
Trans-Activators
Inbred C57BL Mouse
Cell Differentiation
Down-Regulation
Lymph Nodes
Maintenance
Cytokines
Messenger RNA
Membranes
Therapeutics
Genes

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., ... 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

IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow. / Quinci, Angela C.; Vitale, Sara; Parretta, Elisabetta; Soriani, Alessandra; Iannitto, Maria L.; Cippitelli, Marco; Fionda, Cinzia; Bulfone-Paus, Silvia; Santoni, Angela; Di Rosa, Francesca.

In: European Journal of Immunology, Vol. 42, No. 5, 05.2012, p. 1129-1139.

Research output: Contribution to journalArticle

Quinci, AC, Vitale, S, Parretta, E, Soriani, A, Iannitto, ML, 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, vol. 42, no. 5, pp. 1129-1139. https://doi.org/10.1002/eji.201142019
Quinci AC, Vitale S, Parretta E, Soriani A, Iannitto ML, Cippitelli M et al. IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow. European Journal of Immunology. 2012 May;42(5):1129-1139. https://doi.org/10.1002/eji.201142019
Quinci, Angela C. ; Vitale, Sara ; Parretta, Elisabetta ; Soriani, Alessandra ; Iannitto, Maria L. ; Cippitelli, Marco ; Fionda, Cinzia ; Bulfone-Paus, Silvia ; Santoni, Angela ; Di Rosa, Francesca. / IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow. In: European Journal of Immunology. 2012 ; Vol. 42, No. 5. pp. 1129-1139.
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