Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Immunol. 2013 Sep 15;191(6):3119-27. doi: 10.4049/jimmunol.1200938. Epub 2013 Aug 9.
CCR7⁻/⁻ mice exhibit profound anomalies in lymph node and spleen architecture, which complicates the study of CCR7-mediated T cell trafficking in vivo. To circumvent this problem, we established in vivo models in which wild-type and CCR7⁻/⁻ populations coexist within mice possessing normal lymphoid organs and must compete for developmental niches within the tissues of these mice. Under the conditions we have created in vivo, we find the entry of memory CD4 T cells into lymph nodes from the blood to be independent of CCR7. Thus, the central memory CD4 T cells that traffic though lymph nodes, which are often defined by their expression of CCR7, do not appear to gain any competitive homing advantage by expressing this receptor. Furthermore, in contrast to cutaneous dendritic cell populations, we found that CCR7 deficiency had no appreciable effect on the exit of CD4 T cells from inflamed skin. Finally, we found that wild-type and CCR7⁻/⁻ precursors were equally represented within the major thymic subpopulations, despite previous findings that CCR7 plays a role in seeding the thymus from bone marrow-derived T cell precursors.
CCR7⁻/⁻ 小鼠表现出淋巴结和脾脏结构的深刻异常，这使得研究 CCR7 介导的 T 细胞在体内的迁移复杂化。为了规避这个问题，我们建立了体内模型，在这些模型中，野生型和 CCR7⁻/⁻ 群体共存于具有正常淋巴器官的小鼠中，并且必须在这些小鼠组织内竞争发育小生境。在我们在体内创造的条件下，我们发现记忆性 CD4 T 细胞从血液进入淋巴结与 CCR7 无关。因此，通过表达该受体，通过淋巴结迁移的中央记忆性 CD4 T 细胞似乎没有获得任何竞争归巢优势。此外，与皮肤树突状细胞群体相反，我们发现 CCR7 缺陷对 CD4 T 细胞从发炎皮肤的退出没有明显影响。最后，我们发现尽管先前的研究表明 CCR7 在从骨髓源性 T 细胞前体播种胸腺中起作用，但野生型和 CCR7⁻/⁻ 前体在主要胸腺亚群中的代表性相同。
