Characterization of CC-chemokine receptor 7 expression on murine T cells in lymphoid tissues
Characterization of CC-chemokine receptor 7 expression on murine T cells in lymphoid tissues
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DOI：
10.1046/j.1365-2567.2003.01727.x
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发表时间：
2003-10-01
期刊：
影响因子：
6.4
通讯作者：
Thomsen, LL
中科院分区：
文献类型：
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作者：
Bjorkdahl, O;Barber, KA;Thomsen, LL
淋巴结归巢受体和CC趋化因子受体7（CCR7）与L -选择素（CD62L）的表达已被证明可将人类记忆T细胞分为两个功能不同的亚群。我们制备了一种抗鼠CCR7的多克隆抗体，并使用该抗体研究鼠T细胞亚群上的CCR7表达。通过对T细胞进行流式细胞术染色以观察CCR7与CD62L和CD44的表达情况，发现表达CCR7的CD4或CD8 T细胞的主要群体为CD62L（高）CD44（低），这提示为初始细胞表型。与人类研究类似，记忆细胞可细分为CCR7（高）CD62L（高）CD44（高）（中枢记忆）和CCR7（低）CD62L（低）CD44（高）（效应记忆）。这些群体在淋巴结、血液和脾脏中的比例不同。对来自初始小鼠的血液、脾脏和淋巴结细胞进行功能性的短期体外多克隆刺激表明，CCR7（高）CD4 T细胞主要产生白细胞介素（IL）- 2，而CCR7（低）CD4 T细胞产生IL - 2和干扰素 - γ（IFN - γ）。然而，与先前发表的报告相反，CCR7（高）CD8 T细胞亚群产生IFN - γ和IL - 2。对体内免疫诱导的效应T细胞的分析表明，一部分活化的初始CD4 T细胞仅在多次细胞分裂后下调CCR7，这与CD62L的下调以及IL - 4和IFN - γ的产生同时发生。最后，对体内二次免疫应答最大克隆扩增阶段的效应T细胞的分析表明，产生IL - 2和IFN - γ的细胞绝大多数为CCR7（低），而检测到的表达细胞因子的CCR7（高）T细胞很少。我们的结果支持从人类细胞研究中得出的假设，即CCR7可能区分功能不同的鼠记忆T细胞亚群，但也表明存在额外的复杂性，即CCR7（高）CD8 T细胞也可能产生IFN - γ。
Expression of the lymph node homing and CC-chemokine receptor 7 (CCR7), with L-selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T-cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62L(high) CD44(low) which would suggest a naive cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7(high) CD62L high CD44(high) (central memory) and CCR7(low) CD62(low) CD44(high) (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short-term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7(high) CD4 T cells produced predominantly interleukin (IL)-2, whereas CCR7(low) CD4 T cells produced both IL-2 and interferon-gamma (IFN-gamma). However, in contrast to previously published reports, the CCR7(high) CD8 T-cell subpopulation produced both IFN-gamma and IL-2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naive CD4 T cells down-regulated CCR7 only after multiple cell divisions, and this coincided with the down-regulation of CD62L and production of IL-4 and IFN-gamma. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL-2-and IFN-gamma-producing cells are CCR7(low), while few cytokine-expressing CCR7(high) T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T-cell subpopulations, but indicate additional complexity in that CCR7(high) CD8 T cells also may produce IFN-gamma.