Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice.
Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice.
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DOI：
10.1084/jem.187.2.197
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发表时间：
1998-01-19
期刊：
影响因子：
--
通讯作者：
von Andrian UH
中科院分区：
文献类型：
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作者：
Diacovo TG;Catalina MD;Siegelman MH;von Andrian UH
周围淋巴结 (PLN) 对于响应穿透皮肤的抗原而形成免疫记忆至关重要。血源性淋巴细胞通过多步粘附过程归巢到 PLN 后首先遇到此类抗原，该过程通常由高内皮微静脉 (HEV) 中的 L-选择素 (CD62L) 启动。由于在 L-选择素缺陷小鼠中，幼稚 T 细胞无法正常进入 PLN，因此无法对皮肤应用的抗原产生迟发型超敏反应。在这项研究中，我们报告称，将活化的血小板注入 L-选择素敲除小鼠的体循环中，可恢复淋巴细胞向 PLN 的运输，并重建 T 细胞介导的针对皮肤抗原的免疫反应。这些效应需要血小板表达的 P-选择素，使活化的血小板能够在淋巴细胞和 HEV 之间短暂形成桥梁，从而使淋巴细胞能够进行随后的 β2 整合素依赖性牢固粘附。血小板介导的细胞间相互作用对淋巴细胞运输和免疫记忆形成的深远影响可能会影响多种自身免疫和炎症性疾病。
Peripheral lymph nodes (PLN) are critical for immunologic memory formation in response to antigens that penetrate the skin. Blood-borne lymphocytes first encounter such antigens after they home to PLN through a multi-step adhesion process that is normally initiated by L-selectin (CD62L) in high endothelial venules (HEV). Since naive T cells can not enter PLN normally in L-selectin–deficient mice, a delayed type hypersensitivity response to cutaneously applied antigen cannot be mounted. In this study, we report that the administration of activated platelets into the systemic circulation of L-selectin knockout mice restores lymphocyte trafficking to PLN, and reconstitutes T cell–mediated immunity in response to a cutaneous antigen. These effects required platelet-expressed P-selectin that allows activated platelets to transiently form a bridge between lymphocytes and HEV, thereby enabling lymphocytes to undergo subsequent β2 integrin-dependent firm adhesion. These profound effects of platelet-mediated cell–cell interactions on lymphocyte trafficking and formation of immunologic memory may impact on a variety of autoimmune and inflammatory conditions.