Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 42, Issue 5, Pages 1129-1139Publisher
WILEY
DOI: 10.1002/eji.201142019
Keywords
-chain cytokines; T-cell homeostasis; T-cell memory; T-cell recirculation
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Funding
- Italian MIUR (Ministero dell'Istruzione, Universita e Ricerca) [PRIN 20077EYEXN_002]
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CD127 is the IL-7 receptor a-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 CD44high 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 CD44high 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-15Ra 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 CD44high 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 CD44high CD8+ T cells, Foxo1 was not involved in IL-15-induced CD127 downmodulation. Thus, recirculating CD44high 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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