CD8(+)CD28(-) T lymphocytes from HIV-1-infected patients secrete factors that induce endothelial cell proliferation and acquisition of Kaposi's sarcoma cell features.
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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). 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-gamma and TNF-alpha. This finding may have wide implications for our basic understanding of the immunopathology of KS.
Alessandri
Giulio
G
Department of Microbiology, University of Brescia Medical School, Brescia, Italy.
Fiorentini
Simona
S
Licenziati
Stefano
S
Bonafede
Monica
M
Monini
Paolo
P
Ensoli
Barbara
B
Caruso
Arnaldo
A
D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D018106:CD28 Antigens; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D040321:Vascular Endothelial Growth Factor Receptor-3