CD38 and extracellular NAD+ regulate the development and maintenance of Hp vaccine-induced CD4+ TRM in the gastric epithelium.

ABSTRACT

Tissue-resident memory T cells (TRM) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4+ TRM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of TRM. Cluster of differentiation (CD)38 regulated mitochondrial activity and enhanced transforming growth factor-ß signal transduction to promote the differentiation and residence of gastric epithelial CD4+ TRM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of TRM in gastric epithelium by the P2X7 receptor (P2RX7). Vitamin D3 and Gram-positive enhancer matrix (GEM) particles as immune adjuvants combined with Hp vaccination promoted the production of CD69+CD103+CD4+ TRM.