Surface-bound Tat inhibits antigen-specific CD8+ T-cell activation in an integrin-dependent manner.
AIDS
; 28(15): 2189-200, 2014 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-25313583
ABSTRACT
OBJECTIVE:
The identification of still unrevealed mechanisms affecting the anti-HIV CD8 T-cell response in HIV-1 infection.DESIGN:
Starting from the observation that anti-Tat immunization is associated with improved CD8 T-cell immunity, we developed both in-vitro and ex-vivo assays to characterize the effects of extra-cellular Tat on the adaptive CD8 T-cell response.METHODS:
The effects of Tat on CD8 T-cell activation were assayed using CD8 T-cell clones specific for either cellular (MART-1) or viral (HIV-1 Nef) antigens, and HIV-1 Gag-specific CD8 T cells from HIV-1 patients.RESULTS:
The interaction between CD8 T lymphocytes and immobilized Tat, but not its soluble form, inhibits peptide-specific CD8 T-lymphocyte activation. The inhibition does not depend on Tat trans-activation activity, but on the interaction of the Tat RGD domain with α5ß1 and αvß3 integrins. Impaired CD8 T-cell activation was also observed in cocultures of CD8 T cells with HIV-1-infected cells. Anti-Tat Abs abrogate the inhibitory effect, consistently with the evidence that extracellular Tat accumulates on the cell membrane of virus-producing cells. The Tat-induced inhibition of cell activation associates with increased apoptosis of CD8 T cells. Finally, the inhibition of cell activation also takes place in Gag-specific CD8 T lymphocytes from HIV-1-infected patients.CONCLUSION:
Our results support the idea that CD8 T-cell apoptosis induced by surface-bound extracellular Tat can contribute to the dysregulation of the CD8 T-cell adaptive response against HIV as well as other pathogens present in AIDS patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Integrinas
/
HIV-1
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Linfócitos T CD8-Positivos
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Produtos do Gene tat do Vírus da Imunodeficiência Humana
/
Interações Hospedeiro-Patógeno
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
Limite:
Adult
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Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article