Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow
Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow
复制标题
DOI：
10.1016/j.immuni.2009.03.015
复制
发表时间：
2009-05-22
期刊：
影响因子：
32.4
通讯作者：
Radbruch, Andreas
中科院分区：
文献类型：
--
作者：
Tokoyoda, Koji;Zehentmeier, Sandra;Radbruch, Andreas
CD 4（+）T淋巴细胞是免疫记忆的关键。在这里，我们表明，在记忆阶段的特异性免疫反应，大多数的记忆CD 4（+）T淋巴细胞已重新定位到骨髓（BM）在3-8周内，他们的生成-一个过程涉及整合素α 2。抗原特异性记忆性CD 4（+）T淋巴细胞高表达Ly-6C，而不像大多数脾CD 44（hi）CD 62 L（-）CD 4（+）T淋巴细胞。在成年小鼠中，超过80%的Ly-6C（hi）CD 44（hi）CD 62 L（-）记忆性CD 4（+）T淋巴细胞位于BM中。在BM中，它们与表达IL-7的VCAM-1（+）基质相关。细胞基因表达和增殖下调，表明静息状态。在用抗原攻击后，它们迅速表达细胞因子和CD 154，并有效地诱导B淋巴细胞产生高亲和力抗体。因此，在免疫的记忆阶段，记忆辅助T细胞在BM中维持为由表达IL-7的基质细胞限定的存活小生境中的静息但高反应性细胞。
CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha 2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-)CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma. cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.