CD8 + CD28 − CD127 lo CD39 + regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection? Academic Article uri icon

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abstract

  • BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4+ T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4+ T cells/μL. CD8+CD28-CD127loCD39+ T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8+CD28-CD127loCD39+ Treg cells in the circulation of HIV-infected patients. METHODS: The frequency of circulating CD8+CD28-CD127loCD39+ Treg cells was analyzed and correlated with viral load and CD4+ T-cell counts/percentages in 93 HIV-1-infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus-infected patients (n = 17), and healthy donors (n = 173). RESULTS: HIV-infected patients had increased circulating levels of functional CD8+CD28-CD127loCD39+ Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4+ T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non-AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant. CONCLUSION: HIV infection induces remarkable expansion of CD8+CD28-CD127loCD39+ Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.

authors

  • Fenoglio, Daniela
  • Dentone, Chiara
  • Signori, Alessio
  • Di Biagio, Antonio
  • Parodi, Alessia
  • Kalli, Francesca
  • Nasi, Giorgia
  • Curto, Monica
  • Cenderello, Giovanni
  • De Leo, Pasqualina
  • Bartolacci, Valentina
  • Orofino, Giancarlo
  • Nicolini, Laura Ambra
  • Taramasso, Lucia
  • Fiorillo, Edoardo
  • Orrù, Valeria
  • Traverso, Paolo
  • Bruzzone, Bianca
  • Ivaldi, Federico
  • Mantia, Eugenio
  • Guerra, Michele
  • Negrini, Simone
  • Giacomini, Mita
  • Bhagani, Sanjay
  • Filaci, Gilberto

publication date

  • June 2018