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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Research Article Immunology

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 4

Enhanced polyfunctionality as a feature of specific organ-derived Th cells.

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Enhanced polyfunctionality as a feature of specific organ-derived Th cel...
Cytokine expression was assessed in spike-specific Th cells intracellularly by FACS. (A) Frequencies of IFN-γ– or IL-2–positive cells among the indicated paired samples. Liver: n = 8, paired t test; kidney: n = 8, paired t test for IFN-γ and Wilcoxon’s test for IL-2; lung: n = 7, paired t test; bone marrow: n = 10, paired t test; spleen: n = 3, paired t test. (B and C) Simple linear regression analysis of frequencies of specific IFN-γ–expressing (B) or IL-2–expressing (C) Th cells from nonlymphoid tissues versus paired blood. (D and E) Mean frequencies (D) and paired analyses (E) of spike-specific polyfunctional Th cells expressing 3, 2, 1, or 0 of the cytokines IFN-γ, IL-2, and/or IL-4 at a time. Statistically significant differences were tested with paired t test (0–2 cytokines) or with Wilcoxon’s test (3 cytokines). (F and G) Differential IFN-γ or IL-2 expression in spike-specific Th cells from nonlymphoid organs after pre-gating on CD69+ or CD69– (F) and CD49a+ or CD49a– (G) expressing or nonexpressing subsets. Liver: n = 8; kidney: n = 8; lung: n = 7. Statistically significant differences were tested with paired t test (IL-2) or with Wilcoxon’s test (IFN-γ). For D–G, only tissue samples from nonlymphoid organs were included. Red symbols identify vaccinated individuals with a history of SARS-CoV-2 infection that were excluded from statistics.