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Expansion of cytotoxic tissue-resident CD8⁺ T cells and CCR6⁺CD161⁺ CD4⁺ T cells in the nasal mucosa following mRNA COVID-19 vaccination.

ABSTRACT: Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8⁺ T cells expressing CD69⁺CD103⁺ increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log₁₀ cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69⁺CD103⁺CD8⁺ T cells in the blood decrease post-vaccination. Similar increases in nasal CD8⁺CD69⁺CD103^- T cells are observed, particularly following the second dose. CD4⁺ cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8⁺ T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

SUBMITTER: Ssemaganda A

PROVIDER: S-EPMC9186487 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination.

Ssemaganda Aloysious A Nguyen Huong Mai HM Nuhu Faisal F Jahan Naima N Card Catherine M CM Kiazyk Sandra S Severini Giulia G Keynan Yoav Y Su Ruey-Chyi RC Ji Hezhao H Abrenica Bernard B McLaren Paul J PJ Ball T Blake TB Bullard Jared J Van Caeseele Paul P Stein Derek D McKinnon Lyle R LR

Nature communications 20220610 1

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ increase in number ~12 day ...[more]

PMID: 35688805

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Project description:BackgroundSystemic lupus erythematosus (SLE) is a prototypical autoimmune disease affecting multiple organs and tissues with high cellular heterogeneity. CD8+ T cell activity is involved in the SLE pathogenesis. However, the cellular heterogeneity and the underlying mechanisms of CD8+ T cells in SLE remain to be identified.MethodsSingle-cell RNA sequencing (scRNA-seq) of PBMCs from a SLE family pedigree (including 3 HCs and 2 SLE patients) was performed to identify the SLE-associated CD8+ T cell subsets. Flow cytometry analysis of a SLE cohort (including 23 HCs and 33 SLE patients), qPCR analysis of another SLE cohort (including 30 HCs and 25 SLE patients) and public scRNA-seq datasets of autoimmune diseases were employed to validate the finding. Whole-exome sequencing (WES) of this SLE family pedigree was used to investigate the genetic basis in dysregulation of CD8+ T cell subsets identified in this study. Co-culture experiments were performed to analyze the activity of CD8+ T cells.FindingsWe elucidated the cellular heterogeneity of SLE and identified a new highly cytotoxic CD8+ T cell subset, CD161-CD8+ TEMRA cell subpopulation, which was remarkably increased in SLE patients. Meanwhile, we discovered a close correlation between mutation of DTHD1 and the abnormal accumulation of CD161-CD8+ TEMRA cells in SLE. DTHD1 interacted with MYD88 to suppress its activity in T cells and DTHD1 mutation promoted MYD88-dependent pathway and subsequently increased the proliferation and cytotoxicity of CD161-CD8+ TEMRA cells. Furthermore, the differentially expressed genes in CD161-CD8+ TEMRA cells displayed a strong out-of-sample prediction for case-control status of SLE.InterpretationThis study identified DTHD1-associated expansion of CD161-CD8+ TEMRA cell subpopulation is critical for SLE. Our study highlights genetic association and cellular heterogeneity of SLE pathogenesis and provides a mechanistical insight into the diagnosis and treatment of SLE.FundingsStated in the Acknowledgements section of the manuscript.

Dataset Information

Expansion of cytotoxic tissue-resident CD8⁺ T cells and CCR6⁺CD161⁺ CD4⁺ T cells in the nasal mucosa following mRNA COVID-19 vaccination.

Publications

Expansion of cytotoxic tissue-resident CD8<sup>+</sup> T cells and CCR6<sup>+</sup>CD161<sup>+</sup> CD4<sup>+</sup> T cells in the nasal mucosa following mRNA COVID-19 vaccination.

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