The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes
Abstract Background HIV eradication efforts have been unsuccessful partly due to virus persistence in immune sanctuary sites such as germinal centres within lymph node (LN) tissues. Recent evidence suggests that LNs harbour a novel subset of regulatory T cells, termed follicular regulatory T cells (...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12865-022-00508-1 |
| _version_ | 1818242521184075776 |
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| author | Bongiwe Mahlobo Faatima Laher Werner Smidt Funsho Ogunshola Trevor Khaba Thandeka Nkosi Anele Mbatha Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Zaza M. Ndhlovu |
| author_facet | Bongiwe Mahlobo Faatima Laher Werner Smidt Funsho Ogunshola Trevor Khaba Thandeka Nkosi Anele Mbatha Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Zaza M. Ndhlovu |
| author_sort | Bongiwe Mahlobo |
| collection | DOAJ |
| description | Abstract Background HIV eradication efforts have been unsuccessful partly due to virus persistence in immune sanctuary sites such as germinal centres within lymph node (LN) tissues. Recent evidence suggests that LNs harbour a novel subset of regulatory T cells, termed follicular regulatory T cells (TFRs), but their role in HIV pathogenesis is not fully elucidated. Results Paired excisional LN and peripheral blood samples obtained from 20 HIV-uninfected and 31 HIV-infected treated and 7 chronic untreated, were used to determine if and how HIV infection modulate frequencies, function and spatial localization of TFRs within LN tissues. Imaging studies showed that most TFRs are localized in extra-follicular regions. Co-culture assays showed TFRs suppression of TFH help to B cells. Importantly, epigenetic and transcriptional studies identified DPP4 and FCRL3 as novel phenotypic markers that define four functionally distinct TFR subpopulations in human LNs regardless of HIV status. Imaging studies confirmed the regulatory phenotype of DPP4+TFRs. Conclusion Together these studies describe TFRs dynamic changes during HIV infection and reveal previously underappreciated TFR heterogeneity within human LNs. |
| first_indexed | 2024-12-12T13:46:33Z |
| format | Article |
| id | doaj.art-44ea8b47cf83442abec00ae4b385cecd |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-12T13:46:33Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-44ea8b47cf83442abec00ae4b385cecd2022-12-22T00:22:40ZengBMCBMC Immunology1471-21722022-07-0123111910.1186/s12865-022-00508-1The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodesBongiwe Mahlobo0Faatima Laher1Werner Smidt2Funsho Ogunshola3Trevor Khaba4Thandeka Nkosi5Anele Mbatha6Thandekile Ngubane7Krista Dong8Ismail Jajbhay9Johan Pansegrouw10Zaza M. Ndhlovu11Africa Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, University of KwaZulu-NatalHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-NatalKwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-NatalRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard UniversityHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-NatalAfrica Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, University of KwaZulu-NatalHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-NatalHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-NatalRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard UniversityKwaZulu-Natal Department of Health, Prince Mshiyeni Memorial HospitalKwaZulu-Natal Department of Health, Prince Mshiyeni Memorial HospitalAfrica Health Research Institute (AHRI), Nelson R. Mandela School of Medicine, University of KwaZulu-NatalAbstract Background HIV eradication efforts have been unsuccessful partly due to virus persistence in immune sanctuary sites such as germinal centres within lymph node (LN) tissues. Recent evidence suggests that LNs harbour a novel subset of regulatory T cells, termed follicular regulatory T cells (TFRs), but their role in HIV pathogenesis is not fully elucidated. Results Paired excisional LN and peripheral blood samples obtained from 20 HIV-uninfected and 31 HIV-infected treated and 7 chronic untreated, were used to determine if and how HIV infection modulate frequencies, function and spatial localization of TFRs within LN tissues. Imaging studies showed that most TFRs are localized in extra-follicular regions. Co-culture assays showed TFRs suppression of TFH help to B cells. Importantly, epigenetic and transcriptional studies identified DPP4 and FCRL3 as novel phenotypic markers that define four functionally distinct TFR subpopulations in human LNs regardless of HIV status. Imaging studies confirmed the regulatory phenotype of DPP4+TFRs. Conclusion Together these studies describe TFRs dynamic changes during HIV infection and reveal previously underappreciated TFR heterogeneity within human LNs.https://doi.org/10.1186/s12865-022-00508-1Follicular regulatory T cells (TFRs)Follicular helper T (TFH) cellsLymph nodeBiomarkersHIV |
| spellingShingle | Bongiwe Mahlobo Faatima Laher Werner Smidt Funsho Ogunshola Trevor Khaba Thandeka Nkosi Anele Mbatha Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Zaza M. Ndhlovu The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes BMC Immunology Follicular regulatory T cells (TFRs) Follicular helper T (TFH) cells Lymph node Biomarkers HIV |
| title | The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes |
| title_full | The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes |
| title_fullStr | The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes |
| title_full_unstemmed | The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes |
| title_short | The impact of HIV infection on the frequencies, function, spatial localization and heterogeneity of T follicular regulatory cells (TFRs) within human lymph nodes |
| title_sort | impact of hiv infection on the frequencies function spatial localization and heterogeneity of t follicular regulatory cells tfrs within human lymph nodes |
| topic | Follicular regulatory T cells (TFRs) Follicular helper T (TFH) cells Lymph node Biomarkers HIV |
| url | https://doi.org/10.1186/s12865-022-00508-1 |
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