Daniela Fenoglio1, Chiara Dentone2, Alessio Signori3, Antonio Di Biagio4, Alessia Parodi5, Francesca Kalli5, Giorgia Nasi5, Monica Curto5, Giovanni Cenderello6, Pasqualina De Leo7, Valentina Bartolacci8, Giancarlo Orofino9, Laura Ambra Nicolini10, Lucia Taramasso4, Edoardo Fiorillo11, Valeria Orrù11, Paolo Traverso12, Bianca Bruzzone13, Federico Ivaldi5, Eugenio Mantia14, Michele Guerra15, Simone Negrini1, Mauro Giacomini16, Sanjay Bhagani17, Gilberto Filaci18. 1. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 2. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Infectious Diseases Department, Sanremo Hospital, Imperia, Italy. 3. Department of Health Sciences, University of Genoa, Genoa, Italy. 4. Infectious Disease Unit, IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 5. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. 6. Infectious Diseases Department, Galliera Hospital, Genoa, Italy. 7. Infectious Diseases Department, San Paolo Hospital, Savona, Italy. 8. S.M. Misericordia Hospital, Albenga, Italy. 9. Infectious Diseases Department, Amedeo di Savoia Hospital, Turin, Italy. 10. Department of Health Sciences, University of Genoa, Genoa, Italy; Infectious Disease Unit, IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 11. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Sede Secondaria IRGB, Lanusei, Italy. 12. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Department of Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy. 13. Hygiene Unit, Infectious Disease Unit, IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 14. Infectious Diseases Department, SS Antonio, Biagio, Cesare Arrigo Hospital, Alessandria, Italy. 15. Infectious Diseases Department, Sant'Andrea Hospital, La Spezia, Italy. 16. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Informatics, Bioengineering, Robotic and System Engineering, University of Genoa, Genoa, Italy. 17. Department of Infectious Diseases/HIV Medicine, Royal Free Hospital, National Health Service, London, United Kingdom. 18. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. Electronic address: gfilaci@unige.it.
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.
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-infectedpatients. OBJECTIVES: We sought to analyze the frequency of CD8+CD28-CD127loCD39+ Treg cells in the circulation of HIV-infectedpatients. 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-infectedpatients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infectedpatients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus-infectedpatients (n = 17), and healthy donors (n = 173). RESULTS:HIV-infectedpatients 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: Luis Romero-Martín; Ferran Tarrés-Freixas; Núria Pedreño-López; Maria L Rodríguez de la Concepción; Francesc Cunyat; Dennis Hartigan-O'Connor; Jorge Carrillo; Beatriz Mothe; Julià Blanco; Marta Ruiz-Riol; Christian Brander; Alex Olvera Journal: Front Immunol Date: 2022-06-15 Impact factor: 8.786
Authors: Gilberto Filaci; Daniela Fenoglio; Lucia Taramasso; Francesco Indiveri; Antonio Di Biagio Journal: Front Immunol Date: 2018-10-23 Impact factor: 7.561