CXCR5 identifies stem-like resident memory CD8⁺ T cells enriched for latent EBV specificity in tonsils

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• CXCR5+ CD8+ T cells are crucial for antiviral immunity during chronic infections.
• Their precise functions and tissue distribution, especially concerning antigen specificity, require further elucidation.

Purpose of the Study:

• To investigate the anatomical localization and antiviral functions of CXCR5+ CD8+ T cells in various human tissues.
• To focus on oropharyngeal lymphoid tissues, particularly tonsils, for a detailed analysis.

Main Methods:

• Single-cell profiling was employed to analyze T cell populations.
• Tissue distribution and expression of specific markers (CXCR5, Granzyme K, PD-1) were assessed.
• Antigen specificity, including targeting of Epstein-Barr virus (EBV) latent antigens, was examined.

Main Results:

• Tonsils exhibited the highest frequencies of CXCR5+ CD8+ T cells compared to other tissues.
• A significant proportion of these tonsil-resident cells expressed Granzyme K and displayed tissue-resident markers.
• CXCR5 expression was more common on tonsil CD8+ T cells than in circulation, irrespective of clonal identity or virus specificity.
• EBV-specific CD8+ T cells in tonsils frequently expressed CXCR5 and PD-1, indicating a resident stem-like phenotype.

Conclusions:

• A distinct subset of CXCR5+ tissue-resident memory CD8+ T cells is identified in human tonsils.
• These cells possess characteristics suggesting a role in immune surveillance, particularly against EBV.
• The findings advance the understanding of CD8+ T cell heterogeneity and function in mucosal immunity.