Local antigen encounter promotes generation of tissue-resident memory T cells in the large intestine


Upon infection, CD8+ T cells that have been primed in the draining lymph nodes migrate to the invaded tissue, where they receive cues prompting their differentiation into tissue-resident memory cells (Trm), which display niche-specific transcriptional features. Despite the importance of these cells, understanding of their molecular landscape and the signals that dictate their development remains limited, particularly in specific anatomical niches such as the large intestine (LI). Here, the team led by GCIR Professor Simone Becattini, reports that LI Trm generated following oral infection exhibit a distinct transcriptional profile compared to Trm in other tissues. Notably, they observe that local cues play a crucial role in the preferential establishment of LI Trm, favouring precursors that migrate to the tissue early during infection. In this study, the authors identify cognate antigen recognition as a major driver of Trm differentiation at this anatomical site. Local antigen presentation not only promotes the proliferation of effector cells and memory precursors but also facilitates the acquisition of transcriptional features characteristic of gut Trm. Thus, antigen recognition in the LI favours the establishment of Trm by impacting T cell expansion and gene expression.

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Why Is it important?

This study is important because it helps us understand how special immune cells called tissue-resident memory cells (Trm) develop in specific body parts, such as the large intestine, after an infection. Trm cells are generated in the lymph nodes, then migrate to and are retained at the site of infection to provide long-term immunity in the tissue against future invasions by the same pathogen. The research shows that Trm cells in the large intestine have unique characteristics compared to those in other tissues. It also highlights that local signals are crucial for their development. Specifically, although these cells are initially activated by pathogen recognition in the lymph nodes, they need to encounter the pathogen again in the tissue to become Trm and persist long-term. This insight enhances our understanding of immune responses and could potentially guide better vaccine and treatment strategies targeting infections in specific body areas.

23 May 2024