Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8 + T cells.

Autor:	Nguyen S; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Deleage C; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA., Darko S; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Ransier A; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Truong DP; Department of Mathematics, Southern Methodist University, Dallas, TX 75205, USA., Agarwal D; Department of Statistics, University of Pennsylvania, Philadelphia, PA 19104, USA., Japp AS; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Wu VH; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Kuri-Cervantes L; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Abdel-Mohsen M; The Wistar Institute, Philadelphia, PA 19104, USA., Del Rio Estrada PM; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico., Ablanedo-Terrazas Y; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico., Gostick E; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK., Hoxie JA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Zhang NR; Department of Statistics, University of Pennsylvania, Philadelphia, PA 19104, USA., Naji A; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Reyes-Terán G; Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico., Estes JD; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USA.; Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR 97239, USA., Price DA; Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK., Douek DC; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Deeks SG; Department of Medicine, University of California, San Francisco General Hospital, San Francisco, CA 94110, USA., Buggert M; Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden., Betts MR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. betts@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2019 Dec 18; Vol. 11 (523).
DOI:	10.1126/scitranslmed.aax4077
Abstrakt:	The functional properties of circulating CD8 + T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8 + T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8 + T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8 + T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4 + T cell-associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8 + T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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