Characteristics of Splenic CD8αβ ⁺ γδT Cells in Plasmodium yoelii Infection

ABSTRACT γδT cells are a subset of innate lymphocytes that play an essential role in anti‐infection immunity. However, the functional role of CD8αβ + γδT cells, a distinct subset of γδT cells, remains poorly characterized during malaria infection. Female C57BL/6 mice were intraperitoneally injected with 1 × 10 6 Plasmodium yoelii ‐infected red blood cells (iRBCs). At 12 days post‐infection (12 dpi, the peak of parasitemia), spleens were harvested and lymphocytes were isolated. Fluorescence‐activated cell sorting (FACS) was performed to determine the frequency, phenotypic features and functional properties of CD8αβ + γδT cells. Meanwhile, CD45 + lymphocytes were sorted for single‐cell RNA sequencing (scRNA‐seq) to compare differentially expressed genes between CD8αβ + γδT and CD8αα + γδT cell subsets. FACS analysis revealed a significant increase in CD8αβ + γδT cells following P. yoelii infection. These cells exhibited elevated expression of activation‐related molecules, enhanced effector functions, preferential polarization towards an IFN‐γ‐producing (γδT1) phenotype, and reduced expression of exhaustion markers. scRNA‐seq further demonstrated that CD8αβ + γδT cells upregulated genes involved in DNA replication and repair. Our findings indicate that CD8αβ + γδT cells upregulate molecules associated with activation and function during P. yoelii infection, suggesting that they may play a more prominent role in host defence against malaria.