Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes
Summary: CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5− CD4+ T cells with TFH-cell-like features. This CXCR5− subset becomes expanded in severe HIV infection and is characterized by the upregu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719310770 |
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doaj-0d9e7649f1b04057af938988d3c462ca |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Daniel Del Alcazar Yifeng Wang Chenfeng He Ben S. Wendel Perla M. Del Río-Estrada Jerome Lin Yuria Ablanedo-Terrazas Michael J. Malone Stefany M. Hernandez Ian Frank Ali Naji Gustavo Reyes-Terán Ning Jiang Laura F. Su |
| spellingShingle |
Daniel Del Alcazar Yifeng Wang Chenfeng He Ben S. Wendel Perla M. Del Río-Estrada Jerome Lin Yuria Ablanedo-Terrazas Michael J. Malone Stefany M. Hernandez Ian Frank Ali Naji Gustavo Reyes-Terán Ning Jiang Laura F. Su Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes Cell Reports |
| author_facet |
Daniel Del Alcazar Yifeng Wang Chenfeng He Ben S. Wendel Perla M. Del Río-Estrada Jerome Lin Yuria Ablanedo-Terrazas Michael J. Malone Stefany M. Hernandez Ian Frank Ali Naji Gustavo Reyes-Terán Ning Jiang Laura F. Su |
| author_sort |
Daniel Del Alcazar |
| title |
Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes |
| title_short |
Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes |
| title_full |
Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes |
| title_fullStr |
Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes |
| title_full_unstemmed |
Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes |
| title_sort |
mapping the lineage relationship between cxcr5+ and cxcr5− cd4+ t cells in hiv-infected human lymph nodes |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2019-09-01 |
| description |
Summary: CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5− CD4+ T cells with TFH-cell-like features. This CXCR5− subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5−PD-1+ICOS+ T cells revealed a shared clonal relationship with TFH cells. CXCR5−PD-1+ICOS+ T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5−PD-1+ICOS+ T cells to circulating CXCR5− CD4+ T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation. : Follicular helper T (TFH) cells are critical for antibody production. Del Alcazar et al. showed that TFH cells can lose their characteristic chemokine receptor, giving rise to migratory populations of CXCR5− T cells that retain B cell help function and are poised for CXCR5 expression. Keywords: human, mass cytometry, HIV, infection, chronic inflammation, lymph node, follicular helper T cells, T-bet+ B cells, migration |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719310770 |
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doaj-0d9e7649f1b04057af938988d3c462ca2020-11-24T21:58:52ZengElsevierCell Reports2211-12472019-09-01281230473060.e7Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph NodesDaniel Del Alcazar0Yifeng Wang1Chenfeng He2Ben S. Wendel3Perla M. Del Río-Estrada4Jerome Lin5Yuria Ablanedo-Terrazas6Michael J. Malone7Stefany M. Hernandez8Ian Frank9Ali Naji10Gustavo Reyes-Terán11Ning Jiang12Laura F. Su13Department of Medicine, Division of Rheumatology, Philadelphia VA Medical Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Medicine, Division of Rheumatology, Philadelphia VA Medical Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USALaboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USALaboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA; McKetta Department of Chemical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USADepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, MéxicoInstitute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USADepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, MéxicoLaboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, College of Natural Sciences, University of Texas at Austin, Austin, TX 78712, USALaboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA; McKetta Department of Chemical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USADepartment of Medicine, Division of Infectious Disease, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USADepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, MéxicoLaboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, College of Natural Sciences, University of Texas at Austin, Austin, TX 78712, USADepartment of Medicine, Division of Rheumatology, Philadelphia VA Medical Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Corresponding authorSummary: CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5− CD4+ T cells with TFH-cell-like features. This CXCR5− subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5−PD-1+ICOS+ T cells revealed a shared clonal relationship with TFH cells. CXCR5−PD-1+ICOS+ T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5−PD-1+ICOS+ T cells to circulating CXCR5− CD4+ T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation. : Follicular helper T (TFH) cells are critical for antibody production. Del Alcazar et al. showed that TFH cells can lose their characteristic chemokine receptor, giving rise to migratory populations of CXCR5− T cells that retain B cell help function and are poised for CXCR5 expression. Keywords: human, mass cytometry, HIV, infection, chronic inflammation, lymph node, follicular helper T cells, T-bet+ B cells, migrationhttp://www.sciencedirect.com/science/article/pii/S2211124719310770 |