Archivio istituzionale della ricerca dell'Università degli Studi di Palermo
IRIS è il sistema di gestione integrata dei dati della ricerca (persone, pubblicazioni, progetti, attività) adottato dall’Università di Palermo, e ha lo scopo di raccogliere, conservare, documentare, e diffondere ad accesso aperto le informazioni relative alla produzione scientifica degli autori afferenti all’Ateneo.
EnglishRATIONALE: We have investigated the contribution of HLA-A2 and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and HIV-1 co-infection. OBJECTIVE: HIV-1 downregulates HLA-A, -B and -C molecules in infected cells thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E restricted CD8+ T cells due to the inability of the virus to downmodulate their expression. Therefore antigen-specific HLA-E-restricted CD8+ T cells could play a protective response in Mycobacterium tuberculosis and HIV-1 co-infection. METHODS: HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities and their frequencies and phenotypes evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. MEASUREMENTS AND MAIN RESULTS: HIV-1 and Mycobacterium tuberculosis co-infection caused downmodulation of HLA-A2 expression in human monocyte-derived, macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 co-infection, as measured by tetramer staining, but displayed a terminally-differentiated and exhausted phenotype which was rescued in vitro by anti-programmed death-1 monoclonal antibody. CONCLUSIONS: HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 co-infection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking programmed death-1 pathway using the specific monoclonal antibody Nivolumab.
| Data di pubblicazione: | 2019 |
| Titolo: | HLA-E-Restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Co-Infection |
| Autori: | CACCAMO, Nadia Rosalia (Corresponding) |
| Citazione: | La Manna MP, Orlando V, Prezzemolo , Di Carlo P, Cascio A, Delogu G, et al. (2019). HLA-E-Restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Co-Infection. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. |
| Rivista: | |
| Abstract: | RATIONALE: We have investigated the contribution of HLA-A2 and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and HIV-1 co-infection. OBJECTIVE: HIV-1 downregulates HLA-A, -B and -C molecules in infected cells thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E restricted CD8+ T cells due to the inability of the virus to downmodulate their expression. Therefore antigen-specific HLA-E-restricted CD8+ T cells could play a protective response in Mycobacterium tuberculosis and HIV-1 co-infection. METHODS: HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities and their frequencies and phenotypes evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. MEASUREMENTS AND MAIN RESULTS: HIV-1 and Mycobacterium tuberculosis co-infection caused downmodulation of HLA-A2 expression in human monocyte-derived, macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 co-infection, as measured by tetramer staining, but displayed a terminally-differentiated and exhausted phenotype which was rescued in vitro by anti-programmed death-1 monoclonal antibody. CONCLUSIONS: HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 co-infection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking programmed death-1 pathway using the specific monoclonal antibody Nivolumab. |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| rcmb20190261OC_zunw66 signed.pdf | Pre-print | Open Access Visualizza/Apri |
Copyright © 2020