RECRUITMENT OF LYMPHOCYTES DURING CUTANEOUS DELAYED-HYPERSENSITIVITY IN NONHUMAN-PRIMATES IS DEPENDENT ON E-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1

Previous investigations of cutaneous delayed hypersensitivity (DHR) in humans and animals have demonstrated that lymphocyte recruitment from blood is temporally and spatially associated with the de novo, asynchronous expression of both vascular cell adhesion molecule 1 (VCAM-1) and E-selectin on dermal endothelium. In this study, DHR was induced in rhesus monkeys sensitized against tuberculin in order to investigate the contribution of E-selectin and VCAM-1 in lymphocyte recruitment to skin. Intravenous infusions of neutralizing doses of F(ab')(2) fragments of murine antibodies to either E-selectin or VCAM-1 during the early inductive phases of DHR showed that murine IgG localized to dermal endothelium at the site of DHR in a pattern kinetically similar to the expression of each endothelial adhesion protein. Most importantly, the relative numbers of lymphocytes localized to the inflammatory site were significantly reduced in DHR modified with infusions of antibodies to either VCAM-1 or E-selectin, while the numbers of lymphocytes recruited to skin in the animal given F(ab')(2) fragments of an irrelevant murine monoclonal antibody of the same isotype and at the same dose were not changed. Moreover, in individual animals, the relative inhibition achieved with a particular antibody was proportional to the magnitude of expression of the targeted adhesion protein. Therefore, both VCAM-1 and E-selectin are functionally relevant in the genesis of cutaneous DHR, and each appears to contribute to lymphocyte recruitment in relation to its relative degree of expression in any one particular animal.