Epithelial organoid supports resident memory CD8 T cell differentiation

Area of Science:

• Immunology
• Cell Biology
• Organoid Technology

Background:

• Resident Memory T cells (TRM) are crucial for immunity at barrier sites.
• Studying TRM in vivo is challenging due to isolation difficulties and low cell survival.
• Existing models limit high-throughput analysis of TRM biology.

Approach:

• Engineered a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system for in vitro TRM differentiation.
• VEOs mimic vaginal epithelium and induce CD8 T cell differentiation into TRM.
• Confirmed phenotypic and transcriptional similarity of in vitro generated TRM to in vivo TRM.

Key Points:

• In vitro TRM differentiation was reinforced by repeated antigen exposure.
• Soluble factors, particularly TGF-β signaling, are critical for TRM differentiation.
• The model supports viral infection studies and genetic manipulation of CD8 T cells.

Conclusions:

• Established a robust, scalable in vitro model for studying TRM differentiation.
• The model facilitates high-throughput assays for deeper understanding of TRM biology.
• Enables detailed interrogation of antiviral CD8 T cell responses in a reductionist setting.