title: Surface-bound Tat inhibits antigen-specific CD8+ T-cell activation in an integrin-dependent manner.
abstract: OBJECTIVE
  The identification of still unrevealed mechanisms affecting the anti-HIV CD8 T-cell response in HIV-1 infection.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aNational AIDS Center bNational Center for Immunobiologicals, Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy cInstitute of Virology, Helmholtz Zentrum München, German Center for Environmental Health, München, Germany dDepartment of Science, University Roma Tre eIstituti Fisioterapici Ospetalieri, San Gallicano Hospital, Core Laboratory of Virology and Immunology, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Chiozzini
authors.forename: Barbara
authors.initials: B
authors.lastname: Collacchi
authors.forename: Filomena
authors.initials: F
authors.lastname: Nappi
authors.forename: Tanja
authors.initials: T
authors.lastname: Bauer
authors.forename: Claudia
authors.initials: C
authors.lastname: Arenaccio
authors.forename: Antonella
authors.initials: A
authors.lastname: Tripiciano
authors.forename: Olimpia
authors.initials: O
authors.lastname: Longo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ensoli
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Federico
mesh_terms: D000328:Adult; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008297:Male; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D016023:Integrins; D054322:tat Gene Products, Human Immunodeficiency Virus