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Sci Immunol. 2018 Jun 1;3(24). pii: eaar4526. doi: 10.1126/sciimmunol.aar4526.

Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.

Author information

1
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. betts@pennmedicine.upenn.edu marcus.buggert@ki.se.
2
Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
4
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico.
6
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
7
Genome Analysis Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
8
Department of Medicine, Division of Rheumatology, Philadelphia VA Medical Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
10
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
11
Department of Medicine, Perelman School of Medicine, Philadelphia, PA 19104, USA.
12
Department of Medicine, University of California, San Francisco General Hospital, San Francisco, CA 94110, USA.
13
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
14
Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
15
Children's Hospital of Philadelphia, Penn Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
16
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
17
Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
18
Geriatric Research, Education and Clinical Center, Louis Stokes VA Medical Center, Cleveland, OH 44106, USA.
19
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
20
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
21
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Current paradigms of CD8+ T cell-mediated protection in HIV infection center almost exclusively on studies of peripheral blood, which is thought to provide a window into immune activity at the predominant sites of viral replication in lymphoid tissues (LTs). Through extensive comparison of blood, thoracic duct lymph (TDL), and LTs in different species, we show that many LT memory CD8+ T cells bear phenotypic, transcriptional, and epigenetic signatures of resident memory T cells (TRMs). Unlike their circulating counterparts in blood or TDL, most of the total and follicular HIV-specific CD8+ T cells in LTs also resemble TRMs Moreover, high frequencies of HIV-specific CD8+ TRMs with skewed clonotypic profiles relative to matched blood samples are present in LTs of individuals who spontaneously control HIV replication in the absence of antiretroviral therapy (elite controllers). Single-cell RNA sequencing analysis confirmed that HIV-specific TRMs are enriched for effector-related immune genes and signatures compared with HIV-specific non-TRMs in elite controllers. Together, these data indicate that previous studies in blood have largely failed to capture the major component of HIV-specific CD8+ T cell responses resident within LTs.

PMID:
29858286
DOI:
10.1126/sciimmunol.aar4526

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