CD8+CD28-T Lymphocytes from HIV-1-Infected Patients Secrete Factors That Induce Endothelial Cell Proliferation and Acquisition of Kaposi's Sarcoma Cell Features

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Abstract
Kaposi's sarcoma (KS) develops more frequently in human immunodeficiency virus type 1 (HIV-1)-infected patients. In this study, we report that molecules released by CD8+CD28- T lymphocytes from HIV-1-infected patients promote endothelial-cell (EC) growth and induce ECs to acquire spindle cell morphology and upregulation of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular endothelial cell growth factor receptor-3 (VEGFR-3) (a typical feature of the KS cell phenotype). The effects observed on ECs cocultured with in vivo activated CD28- cells were partly reproduced when ECs were grown in medium containing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At concentrations similar to those found in the supernatant of in vivo activated CD28- cells, the two proinflammatory cytokines sustained EC growth and survival only when combined. We, therefore, conclude that CD28- T lymphocytes from HIV-1-infected patients exert their effect on ECs through a mechanism involving both IFN-γ and TNF-α. This finding may have wide implications for our basic understanding of the immunopathology of KS.