Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8(+) T cells.
Blood
; 109(6): 2505-13, 2007 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-17095625
ABSTRACT
What governs the increased apoptosis sensitivity of HIV-specific CD8(+) T cells is poorly understood. Here, we examined the involvement of mitochondria in this apoptosis. Remarkably higher mitochondrial mass (MM) was found in HIV-specific compared with CMV-specific CD8(+) T cells from HIV(+) patients and this could not be attributed to their different differentiation status. MM(High) phenotype characterized those CD8(+) T cells from HIV(+) patients that are sensitive to spontaneous and CD95/Fas-induced apoptosis. CD38 expression did not correlate with high MM, whereas Bcl-2 levels were significantly reduced in both CD38(+) and CD38(-) HIV-specific CD8(+) T cells. Although CD38(+) HIV-specific CD8(+) T cells were more susceptible to apoptosis, CD38 expression does not explain on its own the selective apoptosis sensitivity of HIV-specific CD8(+) T cells, as CD38(-) HIV-specific CD8(+) T cells were more apoptotic than CD38(+) CMV-specific ones. Proapoptotic HIV-specific CD8(+) T cells were CD38(+)Bcl-2(Low)MM(High). Copolarization of mitochondria with CD95/Fas capping, very early in CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells, suggests that mitochondria act as an amplification step for this apoptosis. Thus, an extensive mitochondrial network contributes to apoptosis sensitivity of CD8(+) T cells and, when this occurs together with reduced levels of Bcl-2 and chronic activation, determines the proapoptotic state of HIV-specific CD8(+) T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
HIV
/
Apoptose
/
Linfócitos T CD8-Positivos
/
Dilatação Mitocondrial
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos