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T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC) from gastric biopsies. Classic memory T subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC) obtained from children, adults, and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory T (T EM ) phenotype was observed in gastric LPMC CD4 +  and CD8 +  T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (T RM ) cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8 +  T cells either co-expressed CD103/CD69 (>70%) or expressed CD103 alone (~20%). Gastric LPMC CD4 +  T cells also either co-expressed CD103/CD69 (>35%) or expressed at least one of these markers. Thus, gastric LPMC CD8 +  and CD4 +  T cells had the characteristics of T RM  cells. Gastric CD8 +  and CD4 +  T RM  cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β) and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC T EM  counterparts. Furthermore, gastric CD8 +  T RM  and CD4 +  T RM  cells demonstrated differences in the frequency, susceptibility to activation, and cytokine/multi-cytokine production profiles among the age groups. Most notably, children’s gastric T RM  cells responded differently to stimuli than gastric T RM  cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric T RM , which exhibit diverse functional characteristics in children, adults, and the elderly.

Characterization and Functional Properties of Gastric Tissue-Resident Memory T Cells from Children, Adults, and the Elderly