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IL-15 inhibits IL-7Rα expression by memory-phenotype CD8(+) T cells in the bone marrow.
MedLine Citation:
PMID:  22539288     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Angela C Quinci; Sara Vitale; Elisabetta Parretta; Alessandra Soriani; Maria L Iannitto; Marco Cippitelli; Cinzia Fionda; Silvia Bulfone-Paus; Angela Santoni; Francesca Di Rosa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of immunology     Volume:  42     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1129-39     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Department of Molecular Medicine-Istituto Pasteur Fondazione Cenci-Bolognetti, University of Rome "Sapienza", Rome, Italy; Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche, Rome, Italy.
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