T cell interaction with activated endothelial cells primes for tissue-residency

Area of Science:

• Immunology
• Cell Biology
• Inflammation Research

Background:

• Tissue-resident memory T cells (TRM) are implicated in chronic inflammation, but their development is not fully understood.
• Endothelial cells (EC) interact with T cells entering inflamed tissues, suggesting a potential role in TRM induction.

Purpose of the Study:

• To investigate the effect of cytokine-activated human endothelial cells (EC) on T cell differentiation in vitro.
• To characterize the phenotypic and functional changes in T cells upon interaction with activated EC.

Main Methods:

• Co-culture of human cytokine-activated EC with FACS-sorted T cells.
• Flow cytometry analysis of T cell phenotypes, including CD69 expression and proliferation (CellTrace Violet assay).
• Multiplex immunoassay for soluble mediators.

Main Results:

• Activated EC, but not resting EC, induced CD69 expression on T cells without promoting proliferation or activation markers (CD25, Ki67).
• EC-induced CD69 expression was rapid, stable, and more pronounced on memory T cells, particularly CD8+ effector memory T cells.
• EC-primed T cells exhibited a TRM-like phenotype (e.g., increased CD49a, CD103, CXCR6; decreased CD62L, S1PR1) and enhanced pro-inflammatory cytokine production.

Conclusions:

• Activated EC can induce functional specialization in T cells, characterized by sustained CD69 expression and a TRM-associated phenotype.
• EC-T cell interactions during transmigration into inflamed tissues contribute to the priming of T cells for tissue residency.