IN-VITRO TRANSENDOTHELIAL MIGRATION OF BLOOD T-LYMPHOCYTES FROM HIV-INFECTED INDIVIDUALS

Objective: We hypothesized that differential extravasation of circulat ing CD4+ or CD8+ T lymphocytes contributes to HIV-associated CD8+ lymp hocytic alveolitis. Differences in T-cell transendothelial migration m ay be intrinsic or emerge at sites where vascular endothelium is activ ated by overexpression of tumor necrosis factor (TNF)-alpha and interf eron (IFN)-gamma. Design: We used an in vitro model of lymphocyte extr avasation to assess transendothelial migration of peripheral blood mon onuclear cells (PBMC) from HIV-positive individuals. We assayed bronch oalveolar lavage (BAL) fluid from HIV positive and normal individuals to determine if increased levels of TNF-alpha and IFN-gamma were prese nt in the lungs of HIV-infected individuals. Methods: Transendothelial migration was assessed by determining the number and flow cytometric phenotype of PBMC adherent to or migrating across unstimulated or TNF- alpha and IFN-gamma-activated endothelial cell monolayers. We measured BAL fluid cytokine concentrations using standard antigen-capture enzy me-linked immunosorbent assays for TNF-alpha and IFN-gamma. Results: T cells migrating across unactivated endothelial cells were significant ly enriched for CD4+ T cells. Cytokine activation of endothelial cells allowed significantly greater transendothelial migration of CD8+ T ce lls compared to unactivated endothelial cells. TNF-alpha was increased in BAL fluid from HIV-positive individuals relative to controls. Conc lusions: These data suggest that, in HIV-positive individuals, CD4+ T cells are migration competent and blood CD8+ T cells do not have enhan ced migration competence relative to CD4+ T cells. CD8+ T cell extrava sation is aided by TNF-alpha and IFN-gamma-induced endothelial cells a ctivation.