Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection
CD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, how...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00986/full |
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| author | Alexander Yermanos Alexander Yermanos Ioana Sandu Alessandro Pedrioli Mariana Borsa Franziska Wagen Nathalie Oetiker Suzanne P. M. Welten Katharina Pallmer Sai T. Reddy Annette Oxenius |
| author_facet | Alexander Yermanos Alexander Yermanos Ioana Sandu Alessandro Pedrioli Mariana Borsa Franziska Wagen Nathalie Oetiker Suzanne P. M. Welten Katharina Pallmer Sai T. Reddy Annette Oxenius |
| author_sort | Alexander Yermanos |
| collection | DOAJ |
| description | CD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, however, have been performed using T cell receptor (TCR) transgenic mice, in which CD8 T cells express a monoclonal TCR specific for the LCMV glycoprotein. To investigate whether the Tcf1+ and Tcf1- repertoires are naturally composed of similar or different clones in wild-type mice exposed to acute or chronic LCMV infection, we performed TCR repertoire sequencing of virus-specific CD8 T cells, including Tcf1+ and Tcf1- populations. Our analysis revealed that the Tcf1+ TCR repertoire is maintained at an equal or higher degree of clonal diversity despite harboring fewer cells. Additionally, within the same animal, there was extensive clonal overlap between the Tcf1+ and Tcf1- repertoires in both chronic and acute LCMV infection. We could further detect these virus-specific clones in longitudinal blood samples earlier in the infection. With respect to common repertoire parameters (clonal overlap, germline gene usage, and clonal expansion), we found minor differences between the virus-specific TCR repertoire of acute and chronic LCMV infection 40 days post infection. Overall, our results indicate that the Tcf1+ population emerging during chronic LCMV infection is not clonally distinct from the Tcf1- population, supporting the notion that the Tcf1+ pool is indeed a fuel for the more exhausted Tcf1– population within the heterogenous repertoire of LCMV-specific CD8 T cells. |
| first_indexed | 2024-04-13T16:28:25Z |
| format | Article |
| id | doaj.art-1a477170752c4533a2dbb84ed90972bd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T16:28:25Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1a477170752c4533a2dbb84ed90972bd2022-12-22T02:39:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00986544969Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral InfectionAlexander Yermanos0Alexander Yermanos1Ioana Sandu2Alessandro Pedrioli3Mariana Borsa4Franziska Wagen5Nathalie Oetiker6Suzanne P. M. Welten7Katharina Pallmer8Sai T. Reddy9Annette Oxenius10Department of Biosystems and Engineering, ETH Zurich, Basel, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandDepartment of Biosystems and Engineering, ETH Zurich, Basel, SwitzerlandInstitute of Microbiology, ETH Zurich, Zurich, SwitzerlandCD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, however, have been performed using T cell receptor (TCR) transgenic mice, in which CD8 T cells express a monoclonal TCR specific for the LCMV glycoprotein. To investigate whether the Tcf1+ and Tcf1- repertoires are naturally composed of similar or different clones in wild-type mice exposed to acute or chronic LCMV infection, we performed TCR repertoire sequencing of virus-specific CD8 T cells, including Tcf1+ and Tcf1- populations. Our analysis revealed that the Tcf1+ TCR repertoire is maintained at an equal or higher degree of clonal diversity despite harboring fewer cells. Additionally, within the same animal, there was extensive clonal overlap between the Tcf1+ and Tcf1- repertoires in both chronic and acute LCMV infection. We could further detect these virus-specific clones in longitudinal blood samples earlier in the infection. With respect to common repertoire parameters (clonal overlap, germline gene usage, and clonal expansion), we found minor differences between the virus-specific TCR repertoire of acute and chronic LCMV infection 40 days post infection. Overall, our results indicate that the Tcf1+ population emerging during chronic LCMV infection is not clonally distinct from the Tcf1- population, supporting the notion that the Tcf1+ pool is indeed a fuel for the more exhausted Tcf1– population within the heterogenous repertoire of LCMV-specific CD8 T cells.https://www.frontiersin.org/article/10.3389/fimmu.2020.00986/fullviral infectiondeep sequencingTCF1TCR sequencingadaptive immune receptor repertoire sequencing |
| spellingShingle | Alexander Yermanos Alexander Yermanos Ioana Sandu Alessandro Pedrioli Mariana Borsa Franziska Wagen Nathalie Oetiker Suzanne P. M. Welten Katharina Pallmer Sai T. Reddy Annette Oxenius Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection Frontiers in Immunology viral infection deep sequencing TCF1 TCR sequencing adaptive immune receptor repertoire sequencing |
| title | Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection |
| title_full | Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection |
| title_fullStr | Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection |
| title_full_unstemmed | Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection |
| title_short | Profiling Virus-Specific Tcf1+ T Cell Repertoires During Acute and Chronic Viral Infection |
| title_sort | profiling virus specific tcf1 t cell repertoires during acute and chronic viral infection |
| topic | viral infection deep sequencing TCF1 TCR sequencing adaptive immune receptor repertoire sequencing |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00986/full |
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