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Chiozzini, C.* ; Collacchi, B.* ; Nappi, F.* ; Bauer, T. ; Arenaccio, C.* ; Tripiciano, A.* ; Longo, O.* ; Ensoli, F.* ; Cafaro, A.* ; Ensoli, B.* ; Federico, M.*

Surface-bound Tat inhibits antigen-specific CD8+ T-cell activation in an integrin-dependent manner.

Aids 28, 2189-2200 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 α5β1 and αvβ3 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apoptosis ; Cd8(+) T Cells ; Interferon-gamma ; Integrins ; Tat; Immunodeficiency-virus Type-1; Fibroblast-growth-factor; Heparan-sulfate Proteoglycans; Hiv-1 Tat; Immune-response; Kaposis-sarcoma; Dendritic Cells; Protein; Infection; Aids
ISSN (print) / ISBN 0269-9370
e-ISSN 1473-5571
Journal AIDS
Quellenangaben Volume: 28, Issue: 15, Pages: 2189-2200 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)