CagA-specific gastric CD8+ tissue-resident T cells control Helicobacter pylori during the early infection phase

Infection with Helicobacter pylori strongly impacts global health by causing chronic gastritis, ulcer disease and gastric cancer. Although extensive research into the strong immune response against this persistently colonizing bacterium exists, the specific role of CD8+ T cells remains elusive. We comprehensively characterize gastric H. pylori-specific CD8+ T cell responses in mice and humans. We define CD8+ T cell populations bearing a tissue-resident memory (TRM) phenotype, which infiltrate the gastric mucosa shortly after infection and mediate pathogen control by executing antigen-specific effector properties. These induced CD8+ TRM cells show a skewed T cell receptor beta chain usage and are specific for CagA, the distinctive oncoprotein injected by H. pylori into host cells. As the infection progresses, we observe a loss of the TRM phenotype and replacement of CD8+ by CD4+ T cells, indicating a shift in the immune response during the chronic infection phase. Our results point towards a hitherto unknown role of CD8+ T cell response in this bacterial infection, which may have important clinical implications for treatment and vaccination strategies against H. pylori. Overall design: Gastric CD8+ TRM cells defined by the expression of TCRb, CD8b, CD69 and CD103 as well as control splenic memory T cells defined by the expression of TCRb, CD8b, CD27 and CD44 were isolated from 4 mice infected for 28 days with the H. pylori strain PMSS1. The respective organs were pooled after the creation of single cell suspension, then from each population 10000 cells were sorted for each sample (technical replicates) and bulk RNA-Seq was performed of all samples.