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
Affiliations
Therese Woodring
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
Colin N. Dewey
Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
Lucas Dos Santos Dias
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
Xin He
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
Hannah E. Dobson
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA
Marcel Wüthrich
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA; Corresponding author
Bruce Klein
From the Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA; Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA; Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA; Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison WI, USA; Corresponding author
Summary: 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.
