Surface-bound Tat inhibits antigen-specific CD8+T-cellsactivation in an integrin-dependent manner

Chiara Chiozzini, Barbara Collacchi, Filomena Nappia, Tanja Bauer, Claudia Arenaccioa, Antonella Tripiciano, Olimpia Longo, Fabrizio Ensoli, Aurelio Cafaro, Barbara Ensoli, Maurizio Federico

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The identification of still unrevealed mechanisms affecting the anti-HIV CD8+T- cellsresponse in HIV-1 infection. Design: Starting from the observation that anti-Tat immunization is associated with improved CD8+T- cellsimmunity, we developed both in-vitro and ex-vivo assays to characterize the effects of extra-cellular Tat on the adaptive CD8+T- cells response. Methods: The effects of Tat on CD8+T- cells activation were assayed using CD8+T- cells 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 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- cells apoptosis induced by surface-bound extracellular Tat can contribute to the dysregulation of the CD8+T- cells adaptive response against HIV as well as other pathogens present in AIDS patients.

Original languageEnglish
Pages (from-to)2189-2200
Number of pages12
JournalAIDS (London, England)
Volume28
Issue number15
DOIs
Publication statusPublished - 2014

Keywords

  • Apoptosis
  • CD8<sup>+</sup>T- cells
  • Integrins
  • Interferon-gamma
  • Tat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases
  • Medicine(all)

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