期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 191, 期 1, 页码 77-88出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.191.1.77
关键词
receptors, lymphocyte homing; receptors, chemokine; cell adhesion; endothelium, vascular; lymphoid tissue
资金
- NIAID NIH HHS [AI37832, 5532 AI07290] Funding Source: Medline
- NIGMS NIH HHS [GM37734] Funding Source: Medline
Chemokines have been hypothesized to contribute to the selectivity of lymphocyte trafficking not only as chemoattractants, but also by triggering integrin-dependent sticking (arrest) of circulating lymphocytes at venular sites of extravasation. We show that T cells roll on most Peyer's patch high endothelial venules (PP-HEVs), but preferentially arrest in segments displaying high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine, Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is selectively inhibited by Functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and For macrophage inflammatory protein (MIP)-3 beta (EBV-induced molecule 1 ligand chemokine [ELC]), and does not occur in mutant DDD/1 mice that are deficient in these CCR7 ligands. In contrast, pertussis toxin-sensitive B cell sticking does not require SLC or MIP-3 beta signaling, and occurs efficiently in SLClow/- HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, sites of T and B cell firm adhesion are segregated in PPs, with HEVs supporting B cell accumulation concentrated in or near follicles, the target domain of most B cells entering PPs, whereas T cells preferentially accumulate in interfollicular HEVs. Our findings reveal a Fundamental difference in signaling requirements for PP-HEV recognition by T and B cells, and describe an unexpected level of specialization of HEVs that may allow differential, segmental control of lymphocyte subset recruitment into Functionally distinct lymphoid microenvironments in vivo.
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