Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes
Follicular-helper T cells (TFH) are an essential arm of the adaptive immune system. Although TFH were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex an...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.859070/full |
| _version_ | 1828345127640236032 |
|---|---|
| author | Chenfeng He Michael J. Malone Michael J. Malone Ben S. Wendel Ben S. Wendel Ke-Yue Ma Daniel Del Alcazar Daniel Del Alcazar David B. Weiner Philip L. De Jager Perla M. Del Río-Estrada Yuria Ablanedo-Terrazas Gustavo Reyes-Terán Laura F. Su Laura F. Su Ning Jiang Ning Jiang Ning Jiang Ning Jiang |
| author_facet | Chenfeng He Michael J. Malone Michael J. Malone Ben S. Wendel Ben S. Wendel Ke-Yue Ma Daniel Del Alcazar Daniel Del Alcazar David B. Weiner Philip L. De Jager Perla M. Del Río-Estrada Yuria Ablanedo-Terrazas Gustavo Reyes-Terán Laura F. Su Laura F. Su Ning Jiang Ning Jiang Ning Jiang Ning Jiang |
| author_sort | Chenfeng He |
| collection | DOAJ |
| description | Follicular-helper T cells (TFH) are an essential arm of the adaptive immune system. Although TFH were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing TFH in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of TFH receiving attention in chronic infection are CXCR3-expressing TFH cells (CXCR3+TFH) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other TFH subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of TFH within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3+TFH compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3+TFH away from germinal center TFH (GC-TFH), including the altered expression of several important transcription factors and cytokines. CXCR3+TFH also upregulated cell migration transcriptional programs and were clonally related to peripheral TFH populations. In combination, these data suggest that CXCR3+TFH have a greater tendency to enter circulation than their CXCR3- counterparts, potentially functioning through distinct modalities that may lead to enhanced defense. |
| first_indexed | 2024-04-14T00:07:06Z |
| format | Article |
| id | doaj.art-c4d8069c180c4d2caf8a7868ae973a89 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T00:07:06Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c4d8069c180c4d2caf8a7868ae973a892022-12-22T02:23:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.859070859070Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph NodesChenfeng He0Michael J. Malone1Michael J. Malone2Ben S. Wendel3Ben S. Wendel4Ke-Yue Ma5Daniel Del Alcazar6Daniel Del Alcazar7David B. Weiner8Philip L. De Jager9Perla M. Del Río-Estrada10Yuria Ablanedo-Terrazas11Gustavo Reyes-Terán12Laura F. Su13Laura F. Su14Ning Jiang15Ning Jiang16Ning Jiang17Ning Jiang18Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, United StatesDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United StatesInterdisciplinary Life Sciences Graduate Program, University of Texas at Austin, Austin, TX, United StatesDepartment of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, United StatesMcKetta Department of Chemical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, United StatesInterdisciplinary Life Sciences Graduate Program, University of Texas at Austin, Austin, TX, United StatesDepartment of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA, United StatesCorporal Michael J Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United StatesVaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA, United StatesColumbia University Medical Center, Center for Translational and Computational Neuroimmunology, New York, NY, United StatesDepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, MexicoDepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico0Comisión Coordinadora de Institutos Nacional de Salud y Hospitales de Alta Especialidad, Secretaría de Salud, Ciudad de México, MexicoDepartment of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA, United StatesCorporal Michael J Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United StatesDepartment of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, United StatesDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, United StatesInterdisciplinary Life Sciences Graduate Program, University of Texas at Austin, Austin, TX, United States1Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United StatesFollicular-helper T cells (TFH) are an essential arm of the adaptive immune system. Although TFH were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing TFH in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of TFH receiving attention in chronic infection are CXCR3-expressing TFH cells (CXCR3+TFH) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other TFH subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of TFH within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3+TFH compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3+TFH away from germinal center TFH (GC-TFH), including the altered expression of several important transcription factors and cytokines. CXCR3+TFH also upregulated cell migration transcriptional programs and were clonally related to peripheral TFH populations. In combination, these data suggest that CXCR3+TFH have a greater tendency to enter circulation than their CXCR3- counterparts, potentially functioning through distinct modalities that may lead to enhanced defense.https://www.frontiersin.org/articles/10.3389/fimmu.2022.859070/fullCXCR3follicular-helper T cells (TFH)TCR repertoireRNA-seqHIV |
| spellingShingle | Chenfeng He Michael J. Malone Michael J. Malone Ben S. Wendel Ben S. Wendel Ke-Yue Ma Daniel Del Alcazar Daniel Del Alcazar David B. Weiner Philip L. De Jager Perla M. Del Río-Estrada Yuria Ablanedo-Terrazas Gustavo Reyes-Terán Laura F. Su Laura F. Su Ning Jiang Ning Jiang Ning Jiang Ning Jiang Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes Frontiers in Immunology CXCR3 follicular-helper T cells (TFH) TCR repertoire RNA-seq HIV |
| title | Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes |
| title_full | Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes |
| title_fullStr | Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes |
| title_full_unstemmed | Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes |
| title_short | Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes |
| title_sort | transcriptome and tcr repertoire measurements of cxcr3 t follicular helper cells within hiv infected human lymph nodes |
| topic | CXCR3 follicular-helper T cells (TFH) TCR repertoire RNA-seq HIV |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.859070/full |
| work_keys_str_mv | AT chenfenghe transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT michaeljmalone transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT michaeljmalone transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT benswendel transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT benswendel transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT keyuema transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT danieldelalcazar transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT danieldelalcazar transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT davidbweiner transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT philipldejager transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT perlamdelrioestrada transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT yuriaablanedoterrazas transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT gustavoreyesteran transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT laurafsu transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT laurafsu transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT ningjiang transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT ningjiang transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT ningjiang transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes AT ningjiang transcriptomeandtcrrepertoiremeasurementsofcxcr3tfollicularhelpercellswithinhivinfectedhumanlymphnodes |