The role of chemokines in the microenvironmental control of T versus B cell arrest in Peyer's patch high endothelial venules.
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)-3beta (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-3beta 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.
Warnock
R A
RA
Laboratory of Immunology, Department of Pathology. Stanford University Medical School, Stanford, California, USA.
Campbell
J J
JJ
Dorf
M E
ME
Matsuzawa
A
A
McEvoy
L M
LM
Butcher
E C
EC
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002465:Cell Movement; D054421:Chemokine CCL21; D018925:Chemokines / Q000502:physiology*; D019742:Chemokines, CC / Q000502:physiology; D004729:Endothelium, Lymphatic / Q000166:cytology*; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology*; D051381:Rats; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; C515372:Ccr7 protein, rat; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine