TY - JOUR
T1 - IL-15 inhibits IL-7Rα expression by memory-phenotype CD8 + T cells in the bone marrow
AU - Quinci, Angela C.
AU - Vitale, Sara
AU - Parretta, Elisabetta
AU - Soriani, Alessandra
AU - Iannitto, Maria L.
AU - Cippitelli, Marco
AU - Fionda, Cinzia
AU - Bulfone-Paus, Silvia
AU - Santoni, Angela
AU - Di Rosa, Francesca
PY - 2012/5
Y1 - 2012/5
N2 - 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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
AB - 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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
KW - γ-chain cytokines
KW - T-cell homeostasis
KW - T-cell memory
KW - T-cell recirculation
U2 - 10.1002/eji.201142019
DO - 10.1002/eji.201142019
M3 - Article
C2 - 22539288
SN - 1521-4141
VL - 42
SP - 1129
EP - 1139
JO - European journal of immunology
JF - European journal of immunology
IS - 5
ER -