Killer-cell immunoglobulin-like receptors define a potent effector program in human γδ T cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Human γδ T cells are crucial for immunity but their heterogeneity is not fully understood.
• Killer-cell Immunoglobulin-like Receptors (KIRs) are known on NK cells, but their role on γδ T cells is unexplored.

Purpose of the Study:

• To investigate the functional and molecular relevance of KIR expression on human γδ T cells.
• To identify distinct γδ T cell subsets based on KIR expression.

Main Methods:

• Flow cytometry, ATAC-seq, and RNA-seq were used to analyze γδ T cell subsets.
• KIR expression was assessed as a distinguishing marker.

Main Results:

• KIR expression identified two distinct γδ T cell subsets: KIR⁺ and KIR⁻.
• KIR⁺ γδ T cells showed a memory-like phenotype, enhanced cytotoxicity, and IFNγ production.
• KIR⁻ γδ T cells displayed a naïve-like phenotype and produced IL-17.
• KIR⁺ γδ T cells were enriched in cytomegalovirus (CMV)-seropositive individuals, suggesting antigen-driven expansion.

Conclusions:

• KIR expression defines a functional dichotomy in human γδ T cells, linking IFNγ-driven cytotoxicity with KIR⁺ cells and IL-17 production with KIR⁻ cells.
• This discovery advances understanding of γδ T cell heterogeneity, viral immunity, and immune memory.
• Findings have implications for developing γδ T cell-based immunotherapies.