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. (J. Clin. Invest. 1994Invest. . 93:1554Invest. -1563

This study reports on the endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) in the central nervous system (CNS) early after experimental infection of rhesus monkeys (Macaca mulatta) with pathogenic and nonpathogenic simian immunodeficiency virus (SIV). Diffuse endothelial expression of VCAM-1 was observed in the CNS in all animals receiving pathogenic SIV. These findings demonstrate the rapidity with which pathogenic SIV is able to enter the CNS and induce endothelial cell activation.

Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.