Distinctive populations of CD4+T cells associated with vaccine efficacy

Therese Woodring; Colin N Dewey; Lucas Dos Santos Dias; Xin He; Hannah E Dobson; Marcel Wüthrich; Bruce Klein

doi:10.1016/j.isci.2022.104934

Distinctive populations of CD4⁺T cells associated with vaccine efficacy

iScience. 2022 Aug 13;25(9):104934. doi: 10.1016/j.isci.2022.104934. eCollection 2022 Sep 16.

Authors

Therese Woodring¹, Colin N Dewey², Lucas Dos Santos Dias¹, Xin He¹, Hannah E Dobson¹, Marcel Wüthrich¹, Bruce Klein^{1

3

2

4}

Affiliations

¹ Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA.
² Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA.
³ Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA.
⁴ Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA.

Abstract

Memory T cells underpin vaccine-induced immunity but are not yet fully understood. To distinguish features of memory cells that confer protective immunity, we used single cell transcriptome analysis to compare antigen-specific CD4⁺T cells recalled to lungs of mice that received a protective or nonprotective subunit vaccine followed by challenge with a fungal pathogen. We unexpectedly found populations specific to protection that expressed a strong type I interferon response signature, whose distinctive transcriptional signature appeared unconventionally dependent on IFN-γ receptor. We also detected a unique population enriched in protection that highly expressed the gene for the natural killer cell marker NKG7. Lastly, we detected differences in TCR gene use and in Th1- and Th17-skewed responses after protective and nonprotective vaccine, respectively, reflecting heterogeneous Ifng- and Il17a-expressing populations. Our findings highlight key features of transcriptionally diverse and distinctive antigen-specific T cells associated with protective vaccine-induced immunity.

Keywords: Immune response; Immunology; Transcriptomics.