A Macrophage Colony-Stimulating Factor-Producing gamma-delta T Cell Subset Prevents Malarial Parasitemic Recurrence

Despite evidence that gd T cells play an important role during malaria, their precise role remains unclear. During murine malaria induced by Plasmodium chabaudi infection and in human P. falciparum infection, we found that gd T cells expanded rapidly after resolution of acute parasitemia, in contrast to ab T cells that expanded at the acute stage and then declined. Single-cell sequencing showed that TRAV15N-1 gd T cells were clonally expanded in mice and had convergent complementarity-determining region 3 sequences. These gd T cells expressed specific cytokines, M-CSF, CCL5, CCL3, which are known to act on the myeloid compartment, indicating that this gd T cell subset may have distinct functions. Both gd T cells and M-CSF were necessary for preventing parasitemic recurrence. These findings point to an M-CSF-producing gd T cell subset that fulfills a specialized protective role in the later stage of malaria infection when ab T cells have declined. Total gamma-delta T cells from C57BL/6J mice infected with Plasmodium chabaudi chabaudi AJ strain were collected at 19 days post-infection. RNA was extracted and a library was prepared for sequencing.