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Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.

  • Petrovas C Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. petrovasc@mail.nih.gov.
  • Ferrando-Martinez S Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Gerner MY Laboratory of Systems Biology, Lymphocyte Biology Section, NIAID, NIH, Bethesda, MD 20892, USA.
  • Casazza JP Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Pegu A Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Deleage C AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, MD 21702, USA.
  • Cooper A Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Hataye J Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Andrews S Immunology Core Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Ambrozak D Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Del Río Estrada PM Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
  • Boritz E Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Paris R Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Moysi E Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Boswell KL Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Ruiz-Mateos E Laboratory of Immunovirology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Sevilla 41013, Spain.
  • Vagios I Department of Histopathology, Venizeleio Hospital, Iraklion, Crete, Greece.
  • Leal M Laboratory of Immunovirology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Sevilla 41013, Spain.
  • Ablanedo-Terrazas Y Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
  • Rivero A Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
  • Gonzalez-Hernandez LA Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
  • McDermott AB Immunology Core Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Moir S Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
  • Reyes-Terán G Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
  • Docobo F Laboratory of Immunovirology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Sevilla 41013, Spain.
  • Pantaleo G Service of Immunology and Allergy, Service of Infectious Diseases, Department of Medicine and Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland.
  • Douek DC Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Betts MR Department of Microbiology, Center for AIDS Research, and Institute for Immunology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Estes JD AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, MD 21702, USA.
  • Germain RN Laboratory of Systems Biology, Lymphocyte Biology Section, NIAID, NIH, Bethesda, MD 20892, USA.
  • Mascola JR Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • Koup RA Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
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  • 2017-01-20
Published in:
  • Science translational medicine. - 2017
Adult
Aged
Antibodies, Bispecific
CD8-Positive T-Lymphocytes
Cytokines
Female
Granzymes
HIV Antibodies
HIV Infections
Humans
Lymph Nodes
Male
Middle Aged
Palatine Tonsil
Perforin
Phenotype
English Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals. This profile was associated with persistent local immune activation but did not appear to be directly related to local viral replication. Follicular CD8 (fCD8) T cells, despite compromised cytokine polyfunctionality, showed good cytolytic potential characterized by high ex vivo expression of granzyme B and perforin. We used an anti-HIV/anti-CD3 bispecific antibody in a redirected killing assay and found that fCD8 T cells had better killing activity than did non-fCD8 T cells. Our results indicate that CD8 T cells with potent cytolytic activity are recruited to GCs during HIV infection and, if appropriately redirected to kill HIV-infected cells, could be an effective component of an HIV cure strategy.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/43414
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