The role of chemokines in the micro environmental control of T versus B cell arrest in Peyer's patch high endothelial venules

Chemokines have been hypothesized to contribute to the selectivity of lymph ocyte trafficking not only as chemoattractants, but also by triggering inte grin-dependent sticking (arrest) of circulating lymphocytes at venular site s of extravasation. We show that T cells roll on most Peyer's patch high en dothelial venules (PP-HEVs), but preferentially arrest in segments displayi ng high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine , Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is sel ectively inhibited by Functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and For macrophage inflammatory pr otein (MIP)-3 beta (EBV-induced molecule 1 ligand chemokine [ELC]), and doe s 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 i n wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, s ites of T and B cell firm adhesion are segregated in PPs, with HEVs support ing B cell accumulation concentrated in or near follicles, the target domai n of most B cells entering PPs, whereas T cells preferentially accumulate i n interfollicular HEVs. Our findings reveal a Fundamental difference in sig naling requirements for PP-HEV recognition by T and B cells, and describe a n unexpected level of specialization of HEVs that may allow differential, s egmental control of lymphocyte subset recruitment into Functionally distinc t lymphoid microenvironments in vivo.