SLAMF7 defines subsets of human effector CD8 T cells

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• Long-term viral control depends on memory T cell differentiation into effector T cells during secondary immune responses.
• Progenitor-like effector T cells exist, capable of persisting without antigens and expanding upon re-exposure.

Purpose of the Study:

• To identify specific cell surface markers for progenitor-like effector CD8 T cells and effector CD8 T cells.
• To investigate the role and regulation of these T cell subsets in viral infections and aging.

Main Methods:

• Utilized combinatorial marker analysis (SLAMF7 with CD27, TCF-1, GPR56, TOX) to segregate CD8 T cell subsets.
• Phenotypic and transcriptional characterization of SLAMF7+ CD8 T cells.
• Investigated SLAMF7 pathway dynamics during viral infections, aging, and in response to IL-15 stimulation.

Main Results:

• SLAMF7 combined with CD27 or TCF-1 identifies progenitor-like effector CD8 T cells.
• SLAMF7 combined with GPR56 or TOX identifies effector CD8 T cells.
• SLAMF7+ CD8 T cells are modulated during HIV, HCV, CMV, SARS-CoV-2 infections, and aging, with dysregulated SLAMF7 signaling in aging.
• SLAMF7 ligation with IL-15 induces TCF-1, promoting homeostatic proliferation of progenitor-like effector CD8 T cells.

Conclusions:

• SLAMF7-based markers provide clear identification of distinct effector and progenitor-like effector CD8 T cell populations.
• These subsets play a dynamic role in antiviral immunity and are significantly impacted by the aging process.
• Understanding SLAMF7 pathway regulation is crucial for enhancing T cell-mediated immunity, particularly in the context of aging and chronic infections.