Role of CD4+ T cells in the expansion of the CD4-, CD8- gamma delta T cell subset in the spleens of mice during blood-stage malaria.

The previously observed expansion of the splenic gamma delta T cell subset was examined during the course of murine malaria to determine whether CD4+ T cells are required. Flow cytometric analysis during the course of Plasmodium chabaudi adami malaria in both C57BL/6 and BALB/c mice revealed that the maximal percentage of CD4+ T cells that were blasts occurred during the period of ascending parasitemia, whereas the maximal numbers of gamma delta T cells and blast cells occurred during the period of descending parasitemia. Transfer of enriched populations of CD4+ cells (> 75%) containing < 0.9% gamma delta T cells from immune BALB/c donor to SCID mice led to a population of gamma delta T cells that constituted 37% of the splenic T cells in the recipients and allowed them to resolve their infections. Transfer of the CD4- fraction did not suppress parasitemia. These results suggest that CD4+ T cells are activated early during the infection and are required for the subsequent expansion of the gamma delta T cell population. Furthermore, the maximal gamma delta T cell blast response during the period of descending parasitemia and the detection of high levels of these cells only in models that resolved their infections suggest that these cells may function in the resolution of blood-stage malaria.