Epithelial organoid supports resident memory CD8 T cell differentiation.

Area of Science:

• Immunology
• Cell Biology
• Organoid Technology

Background:

• Resident memory T cells (TRMs) are crucial for localized immune defense.
• Current methods using rodents for TRM research face challenges with cell isolation and survival, limiting high-throughput studies.

Purpose of the Study:

• To establish a robust in vitro system for generating and studying CD8 TRMs.
• To investigate the differentiation process of TRMs in a controlled environment.

Main Methods:

• Development of a co-culture system using murine vaginal epithelial organoids (VEOs) and CD8 T cells.
• Phenotypic and transcriptional analysis of in vitro-generated TRMs.
• Pharmacological and genetic manipulation to study differentiation pathways.

Main Results:

• The VEO-CD8 T cell co-culture system successfully supported CD8 TRM differentiation.
• In vitro-generated TRMs exhibited phenotypic and transcriptional similarity to in vivo TRMs.
• Transforming growth factor β (TGF-β) signaling was identified as critical for TRM differentiation.

Conclusions:

• A scalable and robust in vitro system for TRM differentiation has been established.
• This model system facilitates high-throughput assays for studying TRM biology and antiviral immunity.
• The system allows for detailed interrogation of antiviral CD8 T cell biology within a relevant organoid context.