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Original Article

^a Laboratory of Immunology and Vascular Biology, Department of Pathology,
^b Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, California, 94305
^c Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304
^d Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
^e Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
^f DNAX Research Institute, Palo Alto, California 94304
Department of Pathology L-235, Stanford, CA 94305.650-858-3986650-493-5000 ext. 63130

ebutcher{at}stanford.edu

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)-3β (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-3β signaling, and occurs efficiently in SLC^low/– 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.

Key Words: receptors, lymphocyte homing • receptors, chemokine • cell adhesion • endothelium, vascular • lymphoid tissue

© 2000 The Rockefeller University Press

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