Cervicovaginal Tissue Residence Confers a Distinct Differentiation Program upon Memory CD8 T Cells

Area of Science:

• Immunology
• Microbiology

Background:

• Tissue-resident memory CD8 T cells (CD8 T_RM) are crucial for barrier immunity.
• CD8 T_RM phenotypes are tissue-dependent, with limited understanding in mucosal tissues like the cervicovaginal tract.

Purpose of the Study:

• To investigate the phenotype and maintenance of CD8 T_RM in human and mouse cervicovaginal tissue (CVT).
• To determine if CVT residence is sufficient to induce a specific CD8 T_RM phenotype.

Main Methods:

• Analysis of CD8 T cell populations in human cervicovaginal tissue.
• Utilizing a mouse model with localized and systemic infection to study CD8 T_RM development and maintenance in CVT.
• Phenotypic characterization of CD8 T_RM, including granzyme B and TCF-1 expression.

Main Results:

• Human cervicovaginal CD8 T cells predominantly exhibit a granzyme B-positive (granzyme B⁺) and TCF-1-negative (TCF-1^-) phenotype.
• In the mouse model, CVT CD8 T_RM progressively acquired the granzyme B⁺, TCF-1^- phenotype, mirroring human CVT observations.
• Unlike gut CD8 T_RM, CVT CD8 T_RM were not stably maintained, leading to diminished local immunity.

Conclusions:

• Residence within the cervicovaginal tissue is sufficient to shape the size and function of the CD8 T_RM compartment.
• The cervicovaginal CD8 T_RM compartment exhibits unique characteristics compared to other barrier tissues, potentially impacting local immune responses.