Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus
CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716313997 |
| _version_ | 1828415198922276864 |
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| author | Tiziano Donnarumma George R. Young Julia Merkenschlager Urszula Eksmond Nadine Bongard Stephen L. Nutt Claude Boyer Ulf Dittmer Vu Thuy Khanh Le-Trilling Mirko Trilling Wibke Bayer George Kassiotis |
| author_facet | Tiziano Donnarumma George R. Young Julia Merkenschlager Urszula Eksmond Nadine Bongard Stephen L. Nutt Claude Boyer Ulf Dittmer Vu Thuy Khanh Le-Trilling Mirko Trilling Wibke Bayer George Kassiotis |
| author_sort | Tiziano Donnarumma |
| collection | DOAJ |
| description | CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions. |
| first_indexed | 2024-12-10T13:40:45Z |
| format | Article |
| id | doaj.art-f4bd43170db64a71b16b6a9cf0174c5b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T13:40:45Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f4bd43170db64a71b16b6a9cf0174c5b2022-12-22T01:46:42ZengElsevierCell Reports2211-12472016-11-011761571158310.1016/j.celrep.2016.10.013Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 NexusTiziano Donnarumma0George R. Young1Julia Merkenschlager2Urszula Eksmond3Nadine Bongard4Stephen L. Nutt5Claude Boyer6Ulf Dittmer7Vu Thuy Khanh Le-Trilling8Mirko Trilling9Wibke Bayer10George Kassiotis11Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, GermanyThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaCentre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille 13288, FranceInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, GermanyInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, GermanyInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, GermanyInstitute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, GermanyRetroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKCD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions.http://www.sciencedirect.com/science/article/pii/S2211124716313997cytotoxic CD4 T cellsretroviral infectionadenovirus-based vaccinationsingle-cell RNA sequencinginhibitory receptorsCD4 T cell differentiationantiviral immunity |
| spellingShingle | Tiziano Donnarumma George R. Young Julia Merkenschlager Urszula Eksmond Nadine Bongard Stephen L. Nutt Claude Boyer Ulf Dittmer Vu Thuy Khanh Le-Trilling Mirko Trilling Wibke Bayer George Kassiotis Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus Cell Reports cytotoxic CD4 T cells retroviral infection adenovirus-based vaccination single-cell RNA sequencing inhibitory receptors CD4 T cell differentiation antiviral immunity |
| title | Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus |
| title_full | Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus |
| title_fullStr | Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus |
| title_full_unstemmed | Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus |
| title_short | Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus |
| title_sort | opposing development of cytotoxic and follicular helper cd4 t cells controlled by the tcf 1 bcl6 nexus |
| topic | cytotoxic CD4 T cells retroviral infection adenovirus-based vaccination single-cell RNA sequencing inhibitory receptors CD4 T cell differentiation antiviral immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716313997 |
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