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*
Department of Anatomy and Program in Immunology and
Cardiovascular Research Institute, University of California, San Francisco, CA 94143
The homing of lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines. Secondary lymphoid- tissue chemokine (SLC), a high endothelial venule (HEV)-associated chemokine, has emerged as a candidate for participating in this process. We now show that immobilized SLC strongly induces ß2 integrin-mediated binding of T lymphocytes of naive phenotype and B lymphocytes to ICAM-1 under static conditions. This effect is not mediated by ß2 integrin affinity modulation, because SLC does not elicit a ß2 integrin activation epitope (mAb24) on naive T lymphocytes. In a parallel plate flow chamber, lymphocytes rolling via L-selectin are rapidly arrested through ß2 integrins in a pertussis toxin-sensitive manner on a substrate consisting of L-selectin ligands (peripheral lymph node addressins) together with ICAM-1 and SLC. Naive T lymphocytes are arrested on the HEV substrate with sixfold higher efficiency than memory cells. Neutrophils roll, but are not arrested by SLC, whereas they respond to immobilized IL-8 with rapid arrest. Thus, our artificial HEV system recapitulates critical features of lymphocyte interactions with HEV in vivo. These observations strongly point to the participation of SLC in homing of lymphocytes to secondary lymphoid organs.
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