SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues
Vanessa Proß, … , Christian Conrad, Katja Kotsch
Vanessa Proß, … , Christian Conrad, Katja Kotsch
Published October 10, 2023
Citation Information: J Clin Invest. 2023;133(24):e171797. https://doi.org/10.1172/JCI171797.
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SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues

Abstract

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine–specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

Authors

Vanessa Proß, Arne Sattler, Sören Lukassen, Laura Tóth, Linda Marie Laura Thole, Janine Siegle, Carolin Stahl, An He, Georg Damm, Daniel Seehofer, Christina Götz, Christian Bayerl, Pia Jäger, Alexander Macke, Stephan Eggeling, Bernadette Kirzinger, Thomas Mayr, Hermann Herbst, Katharina Beyer, Dominik Laue, Jan Krönke, Jan Braune, Friederike Rosseck, Beatrice Kittner, Frank Friedersdorff, Mandy Hubatsch, Sarah Weinberger, Nils Lachmann, Veit Maria Hofmann, Eva Schrezenmeier, Carolin Ludwig, Hubert Schrezenmeier, Katharina Jechow, Christian Conrad, Katja Kotsch

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Figure 7

Shared TCR clonotypes between tissues.

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Shared TCR clonotypes between tissues. (A) Heatmap depicting the overlap...
(A) Heatmap depicting the overlap in absolute numbers of CDR3 sequences in different samples. (B) Percentage of cells with at least 1 of the 10 most frequent clonotypes per sample, colored by organ. Total cell numbers with known clonotype are indicated above the bars. Blood and liver samples from donors 1–4 were paired, whereas samples 5–12 were from different donors. (C) Association of clonotypes with gene expression. UMAP plots with cells that have a shared clonotype highlighted in red. Separate graphs for all 9 different clonotypes with at least 4 cells (inclusion criterion) are shown. (D) Impact of shared versus different metadata on the cell-cell Spearman’s correlation coefficient for highly variable genes. Mean change and 95% confidence intervals were obtained using Tukey’s honestly significant difference test, considering all individual variables as well as their interactions. (E) log2 odds ratio for clonotypes or CDR3 sequences shared between blood and liver in liver-derived cells positive versus negative for CD49a (top) or CD103 (bottom). Positivity for these markers was defined as the presence of at least 1 count of the respective molecule. Whiskers extend to the 95% confidence interval.