TY - JOUR
T1 - CagA-specific Gastric CD8+ Tissue-Resident T Cells Control Helicobacter pylori During the Early Infection Phase
AU - Koch, Maximilian R.A.
AU - Gong, Ruolan
AU - Friedrich, Verena
AU - Engelsberger, Veronika
AU - Kretschmer, Lorenz
AU - Wanisch, Andreas
AU - Jarosch, Sebastian
AU - Ralser, Anna
AU - Lugen, Bob
AU - Quante, Michael
AU - Vieth, Michael
AU - Vasapolli, Riccardo
AU - Schulz, Christian
AU - Buchholz, Veit R.
AU - Busch, Dirk H.
AU - Mejías-Luque, Raquel
AU - Gerhard, Markus
N1 - Publisher Copyright:
© 2023 AGA Institute
PY - 2023/4
Y1 - 2023/4
N2 - Background & Aims: Infection with Helicobacter pylori strongly affects 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. Methods: We comprehensively characterize gastric H pylori–specific CD8+ T-cell responses in mice and humans by flow cytometry, RNA-sequencing, immunohistochemistry, and ChipCytometry, applying functional analyses including T-cell depletion, H pylori eradication, and ex vivo restimulation. Results: 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+ tissue-resident memory T cells (TRM cells) show a skewed T-cell receptor beta chain usage and are mostly specific for cytotoxin-associated gene A, 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. Conclusions: Our results point toward 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.
AB - Background & Aims: Infection with Helicobacter pylori strongly affects 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. Methods: We comprehensively characterize gastric H pylori–specific CD8+ T-cell responses in mice and humans by flow cytometry, RNA-sequencing, immunohistochemistry, and ChipCytometry, applying functional analyses including T-cell depletion, H pylori eradication, and ex vivo restimulation. Results: 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+ tissue-resident memory T cells (TRM cells) show a skewed T-cell receptor beta chain usage and are mostly specific for cytotoxin-associated gene A, 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. Conclusions: Our results point toward 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.
KW - CD8 T Cells
KW - Helicobacter pylori
KW - Mucosal Defense
KW - Tissue-resident T Cells
UR - http://www.scopus.com/inward/record.url?scp=85148734153&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2022.12.016
DO - 10.1053/j.gastro.2022.12.016
M3 - Article
C2 - 36587707
AN - SCOPUS:85148734153
SN - 0016-5085
VL - 164
SP - 550
EP - 566
JO - Gastroenterology
JF - Gastroenterology
IS - 4
ER -