Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

Area of Science:

• Immunology
• Cell Biology
• Gastroenterology

Background:

• Tissue-resident memory T (T_RM) cells are crucial for adaptive immunity against pathogens, cancer, and autoimmune diseases.
• The transcriptional landscape and functional diversity of human intestinal T_RM cells are not fully understood.

Purpose of the Study:

• To investigate the transcriptional and functional heterogeneity of human intestinal T_RM cells.
• To identify distinct subsets within human intestinal CD4⁺ and CD8⁺ T_RM populations.

Main Methods:

• Single-cell transcriptional profiling of donor-derived T_RM cells from intestinal transplant recipients.
• Flow cytometry analysis of recipient-derived cells and lymphocytes from healthy gut.
• Analysis of gene expression related to cytotoxicity and cell residency.

Main Results:

• Two distinct transcriptional states of CD8⁺ T_RM cells were identified, defined by ITGAE and ITGB2 expression.
• CD8⁺ CD69⁺CD103⁺ T_RM cells produced IL-2 and exhibited polyfunctional cytokine production.
• β2-integrin⁺ CD69⁺CD103^- T_RM cells showed higher granzyme expression.
• Parallels were observed in intestinal CD4⁺ T cells, including a β2-integrin⁺ population.

Conclusions:

• This study elucidates the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4⁺ and CD8⁺ T_RM cells.
• The identified T_RM cell subsets possess distinct functional characteristics relevant to gut immunity.