CD8+CD28CD127loCD39+ regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?

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

Research output: Contribution to journalArticle

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+CD28CD127loCD39+ 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+CD28CD127loCD39+ Treg cells in the circulation of HIV-infected patients. Methods: The frequency of circulating CD8+CD28CD127loCD39+ 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+CD28CD127loCD39+ 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+CD28CD127loCD39+ 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.

Original languageEnglish
Pages (from-to)2220-2233.e4
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Regulatory T-Lymphocytes
HIV Infections
HIV
T-Lymphocytes
Viremia
CD4 Lymphocyte Count
Human Immunodeficiency Virus Proteins
Tumor Microenvironment
Hepatitis C
Viral Load
Neoplasms
Acquired Immunodeficiency Syndrome
Chronic Disease
Therapeutics
Biomarkers
Tissue Donors
Antigens

Keywords

  • antiretroviral therapy
  • CD8CD28CD127CD39 regulatory T cell
  • HIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

CD8+CD28CD127loCD39+ regulatory T-cell expansion : A new possible pathogenic mechanism for HIV infection? / 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, Mauro; Bhagani, Sanjay; Filaci, Gilberto.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 6, 01.06.2018, p. 2220-2233.e4.

Research output: Contribution to journalArticle

Fenoglio, D, Dentone, C, Signori, A, Di Biagio, A, Parodi, A, Kalli, F, Nasi, G, Curto, M, Cenderello, G, De Leo, P, Bartolacci, V, Orofino, G, Nicolini, LA, Taramasso, L, Fiorillo, E, Orrù, V, Traverso, P, Bruzzone, B, Ivaldi, F, Mantia, E, Guerra, M, Negrini, S, Giacomini, M, Bhagani, S & Filaci, G 2018, 'CD8+CD28CD127loCD39+ regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?', Journal of Allergy and Clinical Immunology, vol. 141, no. 6, pp. 2220-2233.e4. https://doi.org/10.1016/j.jaci.2017.08.021
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, Mauro ; Bhagani, Sanjay ; Filaci, Gilberto. / CD8+CD28CD127loCD39+ regulatory T-cell expansion : A new possible pathogenic mechanism for HIV infection?. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 6. pp. 2220-2233.e4.
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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.",
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T1 - CD8+CD28−CD127loCD39+ regulatory T-cell expansion

T2 - A new possible pathogenic mechanism for HIV infection?

AU - Fenoglio, Daniela

AU - Dentone, Chiara

AU - Signori, Alessio

AU - Di Biagio, Antonio

AU - Parodi, Alessia

AU - Kalli, Francesca

AU - Nasi, Giorgia

AU - Curto, Monica

AU - Cenderello, Giovanni

AU - De Leo, Pasqualina

AU - Bartolacci, Valentina

AU - Orofino, Giancarlo

AU - Nicolini, Laura Ambra

AU - Taramasso, Lucia

AU - Fiorillo, Edoardo

AU - Orrù, Valeria

AU - Traverso, Paolo

AU - Bruzzone, Bianca

AU - Ivaldi, Federico

AU - Mantia, Eugenio

AU - Guerra, Michele

AU - Negrini, Simone

AU - Giacomini, Mauro

AU - Bhagani, Sanjay

AU - Filaci, Gilberto

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

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KW - CD8CD28CD127CD39 regulatory T cell

KW - HIV

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