Mapping the Lineage Relationship between CXCR5+ and CXCR5− CD4+ T Cells in HIV-Infected Human Lymph Nodes
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
Affiliations
Daniel Del Alcazar
Department 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
Yifeng Wang
Department 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
Chenfeng He
Laboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA
Ben S. Wendel
Laboratory 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, USA
Perla M. Del Río-Estrada
Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, México
Jerome Lin
Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA
Yuria Ablanedo-Terrazas
Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, México
Michael J. Malone
Laboratory 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, USA
Stefany M. Hernandez
Laboratory 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, USA
Ian Frank
Department of Medicine, Division of Infectious Disease, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Ali Naji
Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Gustavo Reyes-Terán
Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, México
Ning Jiang
Laboratory 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, USA
Laura F. Su
Department 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 author
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
