Distinctive populations of CD4+T cells associated with vaccine efficacy

Memory T cells underpin vaccine-induced immunity but are not yet fully under-stood. 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 uncon-ventionally dependent on IFN-g 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, respec-tively, reflecting heterogeneous Ifng- and Il17a-expressing populations. Our find-ings highlight key features of transcriptionally diverse and distinctive antigen -specific T cells associated with protective vaccine-induced immunity.