{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:45:57Z","timestamp":1790660757780,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E\u2013restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I\u2013restricted CD8+ T cells but not by HLA-E\u2013restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E\u2013restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E\u2013 and HLA-A2\u2013restricted Mycobacterium tuberculosis\u2013specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte\u2013derived macrophages associated with resistance to lysis by HLA-A2\u2013restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E\u2013restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E\u2013restricted and Mycobacterium tuberculosis\u2013specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis\/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti\u2013PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E\u2013restricted and Mycobacterium tuberculosis\u2013specific CD8+ T cells in patients with Mycobacterium tuberculosis\/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0261oc","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T16:15:51Z","timestamp":1573143351000},"page":"430-439","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":22,"title":["HLA-E\u2013restricted CD8+ T Lymphocytes Efficiently Control\n                    <i>Mycobacterium tuberculosis<\/i>\n                    and HIV-1 Coinfection"],"prefix":"10.1093","volume":"62","author":[{"given":"Marco Pio","family":"La Manna","sequence":"first","affiliation":[{"name":"Central Laboratory for Advanced Diagnosis and Biomedical Research"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Orlando","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnosis and Biomedical Research"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Prezzemolo","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnosis and Biomedical Research"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Department of Sciences for Health Promotion and Mother-Child Care \u201cG. D\u2019Alessandro,\u201d University of Palermo, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Department of Sciences for Health Promotion and Mother-Child Care \u201cG. D\u2019Alessandro,\u201d University of Palermo, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Delogu","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Catholic University of the Sacred Heart, Rome, Italy"},{"name":"Foundation Policlinico Universitario Gemelli, Institute for Scientific-based Care and Research (IRCCS) Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Poli","sequence":"additional","affiliation":[{"name":"AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milano, Italy"},{"name":"Vita-Salute San Raffaele University School of Medicine, Milano, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy C.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Dieli","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnosis and Biomedical Research"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Caccamo","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnosis and Biomedical Research"},{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, 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