Bone marrow CD8 cells down-modulate membrane IL-7Rα expression and exhibit increased STAT-5 and p38 K phosphorylation in the organ environment
Bone marrow CD8 cells down-modulate membrane IL-7Rα expression and exhibit increased STAT-5 and p38 K phosphorylation in the organ environment
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DOI：
10.1182/blood-2006-09-045807
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Di Rosa, Francesca
中科院分区：
文献类型：
--
作者：
Cassese, Giuliana;Parretta, Elisabetta;Di Rosa, Francesca
通过比较成熟的CD 8细胞在不同器官中的周转，我们以前证明了CD 8细胞主要在骨髓（BM）中增殖。为了研究这种增加的转换的潜在机制，我们比较了来自未处理的C57 BU 6小鼠的BM、淋巴结和脾CD 8细胞在器官内的体内增殖;对白细胞介素-7（IL-7）、IL-15、IL-21的体外应答;膜CD 127的离体表达（IL-7 R α），细胞内Bcl-2，磷酸化STAT-5（信号转导子和转录激活子5）、磷酸-p38丝裂原激活蛋白激酶（MAPK）;和过继转移的体内增殖。在BM中，总CDS细胞或单个CD 44和CD 122亚群的增殖率增加。相反，与相应的脾细胞相比，从BM纯化的CD 8（+）细胞对IL-7、IL-15和IL-21的体外增殖反应没有增强。转移和聚肌苷酸-聚胞苷酸（polyI：C）治疗后，脾衍生和BM衍生的CD 8细胞从同源供体增殖约两倍以上的受体BM比脾和淋巴结。我们的研究结果表明，BM CD 8细胞并不致力于自我更新，而是在器官中受到刺激。在未处理小鼠的BM内的CD 8细胞中不断诱导的分子事件包括磷酸化STAT-5和磷酸化p38细胞内水平的增加以及CD 127膜表达的减少。
By comparing mature CD8-cell turnover in different organs, we previously demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To investigate the mechanisms underlying such increased turnover, we compared BM, lymph nodes, and spleen CD8 cells from untreated C57BU6 mice regarding in vivo proliferation within the organ; in vitro response to interleukin-7 (IL-7), IL-15, IL-21; ex vivo expression of membrane CD127 (IL-7R alpha), intracellular Bcl-2, phospho-STAT-5 (signal transducer and activator of transcription 5), phospho-p38 mitogen activated protein kinase (MAPK); and in vivo proliferation on adoptive transfer. In the BM, the proliferation rate was increased for either total CDS cells or individual CD44 and CD122 subsets. In contrast, purified CD8(+) cells from the BM did not show an enhanced in vitro proliferative response to IL-7, IL-15, and IL-21 compared with corresponding spleen cells. After transfer and polyinosinic-polycytidylic acid (polyl:C) treatment, both spleen-derived and BM-derived CD8 cells from congenic donors proliferated approximately twice more in the recipient BM than in spleen and lymph nodes. Our results suggest that BM CD8 cells are not committed to self-renewal, but rather are stimulated in the organ. Molecular events constantly induced in the CD8 cells within the BM of untreated mice include increase of both phosphorylated STAT-5 and phosphorylated p38 intracellular levels, and the reduction of CD127 membrane expression.