Background: Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Attempts to develop a vaccine have not been successful, partly due to the absence of well-defined immune correlates of protection. The inflammatory response to H. pylori infection is characterised by the recruitment of T cells expressing markers of tissue-resident memory T (TRM) cells to the gastric mucosa. However, the function of TRM cells in gastric tissue during H. pylori reinfection remained poorly understood.
Objective: We aimed to investigate the induction, development and function of gastric TRM cells during primary and secondary H. pylori infection.
Design: We characterised gastric H. pylori-specific TRM cells in mice and humans by flow cytometry, immunohistochemistry, immunofluorescence, ChipCytometry staining and single-cell RNA sequencing. The function of gastric TRM cells was established in H. pylori eradication and reinfection experiments as well as by targeted depletion of Hobit+ TRM cells and neutrophils in mice.
Results: Expression of the transcription factor Hobit governs the induction and development of gastric TRM cells, which largely depend on the presence of the H. pylori virulence factor Cytotoxin-associated gene A. H. pylori-specific CD4+ and CD8+ TRM cells resided long-term in the stomach and conferred complete protection from reinfection with the help of neutrophils. Gastric CD8+ TRM cells exhibited varying Hobit expression levels and clustered into distinct subgroups based on distinct transcriptomic and cytokine profiles, suggesting functional specialisation.
Conclusion: These findings establish gastric TRM cells as bona fide correlates of protection against H. pylori, highlighting their potential for future prophylactic and therapeutic strategies.
Keywords: GUT IMMUNOLOGY; HELICOBACTER PYLORI; MUCOSAL IMMUNOLOGY; T LYMPHOCYTES.
© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.