| IL-15 inhibits IL-7Rα expression by memory-phenotype CD8(+) T cells in the bone marrow. | |
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MedLine Citation:
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PMID: 22539288 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: European journal of immunology Volume: 42 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 1129-39 Citation Subset: IM |
Copyright Information:
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© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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