HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8(+) T cells producing both interferon-gamma and tumor necrosis factor-alpha.
Blood
; 104(2): 487-94, 2004 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-15059848
ABSTRACT
CD8(+) T cells play a crucial role in the control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. Recent data suggest that HIV-1-specific CD8(+) T cell subsets may differ in their ability to exert these effector functions. Here, we directly compared the cytokine secretion patterns and cytotoxic capacity of HIV-1-specific CD8(+) T cells, using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells. These experiments revealed considerable intraindividual and interindividual differences among epitope-specific T-cell effector functions while the frequency of HIV-1-specific CD8(+) T cells secreting interferon-gamma but no tumor necrosis factor-alpha (TNF-alpha) following antigenic stimulation was only weakly correlated to their cytotoxic activity (R = 0.05, P =.57), a subset of CD8(+) T cells secreting both inter-feron-gamma and TNF-alpha was substantially more strongly associated with cytotoxicity (R = 0.67, P <.001). This subset of CD8(+) T cells also exhibited stronger intracellular perforin expression and more pronounced direct ex vivo HIV-1-specific cytoxicity than CD8(+) T cells secreting solely interferon-gamma following sorting of these subpopulations according to their cytokine profile. These results suggest that HIV-1-specific cytotoxicity of CD8(+) T cells is preferentially mediated by a subset of CD8(+) T cells secreting both interferon-gamma and TNF-alpha.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Interferon gama
/
Fator de Necrose Tumoral alfa
/
Linfócitos T CD8-Positivos
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article