Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection
Although recent evidence indicates that CD4+ T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterpa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/80079 |
| _version_ | 1797991278992949248 |
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| author | Ryan Zander Achia Khatun Moujtaba Y Kasmani Yao Chen Weiguo Cui |
| author_facet | Ryan Zander Achia Khatun Moujtaba Y Kasmani Yao Chen Weiguo Cui |
| author_sort | Ryan Zander |
| collection | DOAJ |
| description | Although recent evidence indicates that CD4+ T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterparts remains unclear. Additionally, whether cell-intrinsic factors such as TCR usage influence CD4+ T cell fate commitment during persistent infection has not previously been studied. Herein, we perform single-cell RNA sequencing (scRNA-seq) combined with single-cell T cell receptor sequencing (scTCR-seq) on virus-specific CD4+ T cells isolated from mice infected with chronic lymphocytic choriomeningitis virus (LCMV) infection. We identify several transcriptionally distinct states among the Th1, Tfh, and memory-like T cell subsets that form at the peak of infection, including the presence of a previously unrecognized Slamf7+ subset with cytolytic features. We further show that the relative distribution of these populations differs substantially between acute and persistent LCMV infection. Moreover, while the progeny of most T cell clones displays membership within each of these transcriptionally unique populations, overall supporting a one cell-multiple fate model, a small fraction of clones display a biased cell fate decision, suggesting that TCR usage may impact CD4+ T cell development during chronic infection. Importantly, comparative analyses further reveal both subset-specific and core gene expression programs that are differentially regulated between CD4+ T cells responding to acute and chronic LCMV infection. Together, these data may serve as a useful framework and allow for a detailed interrogation into the clonal distribution and transcriptional circuits underlying CD4+ T cell differentiation during chronic viral infection. |
| first_indexed | 2024-04-11T08:49:35Z |
| format | Article |
| id | doaj.art-610c1c6f4f8b4e36b1969d0efefb8e1a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T08:49:35Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-610c1c6f4f8b4e36b1969d0efefb8e1a2022-12-22T04:33:50ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.80079Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infectionRyan Zander0https://orcid.org/0000-0002-7431-8535Achia Khatun1Moujtaba Y Kasmani2https://orcid.org/0000-0002-5753-5335Yao Chen3Weiguo Cui4https://orcid.org/0000-0003-1562-9218Blood Research Institute, Versiti Wisconsin, Milwaukee, United StatesBlood Research Institute, Versiti Wisconsin, Milwaukee, United States; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, United StatesBlood Research Institute, Versiti Wisconsin, Milwaukee, United States; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, United StatesBlood Research Institute, Versiti Wisconsin, Milwaukee, United States; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, United StatesBlood Research Institute, Versiti Wisconsin, Milwaukee, United States; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, United StatesAlthough recent evidence indicates that CD4+ T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterparts remains unclear. Additionally, whether cell-intrinsic factors such as TCR usage influence CD4+ T cell fate commitment during persistent infection has not previously been studied. Herein, we perform single-cell RNA sequencing (scRNA-seq) combined with single-cell T cell receptor sequencing (scTCR-seq) on virus-specific CD4+ T cells isolated from mice infected with chronic lymphocytic choriomeningitis virus (LCMV) infection. We identify several transcriptionally distinct states among the Th1, Tfh, and memory-like T cell subsets that form at the peak of infection, including the presence of a previously unrecognized Slamf7+ subset with cytolytic features. We further show that the relative distribution of these populations differs substantially between acute and persistent LCMV infection. Moreover, while the progeny of most T cell clones displays membership within each of these transcriptionally unique populations, overall supporting a one cell-multiple fate model, a small fraction of clones display a biased cell fate decision, suggesting that TCR usage may impact CD4+ T cell development during chronic infection. Importantly, comparative analyses further reveal both subset-specific and core gene expression programs that are differentially regulated between CD4+ T cells responding to acute and chronic LCMV infection. Together, these data may serve as a useful framework and allow for a detailed interrogation into the clonal distribution and transcriptional circuits underlying CD4+ T cell differentiation during chronic viral infection.https://elifesciences.org/articles/80079CD4+ T cell differentiationchronic viral infectionscRNAseq |
| spellingShingle | Ryan Zander Achia Khatun Moujtaba Y Kasmani Yao Chen Weiguo Cui Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection eLife CD4+ T cell differentiation chronic viral infection scRNAseq |
| title | Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection |
| title_full | Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection |
| title_fullStr | Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection |
| title_full_unstemmed | Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection |
| title_short | Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection |
| title_sort | delineating the transcriptional landscape and clonal diversity of virus specific cd4 t cells during chronic viral infection |
| topic | CD4+ T cell differentiation chronic viral infection scRNAseq |
| url | https://elifesciences.org/articles/80079 |
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