Splenic γδ T Cells Regulated by CD4⁺T Cells Are Required To Control ChronicPlasmodium chabaudiMalaria in the B-Cell-Deficient Mouse

Abstract

Little is known about the function and regulation of splenic ␥␦ T cells during chronic

γδ T Cells but Not NK Cells Are Essential for Cell-Mediated Immunity against Plasmodium chabaudi Malaria

“…During experimental P. chabaudi malaria, the depletion of ␥␦ T cells from WT mice results in significantly elevated parasitemia at several time points prior to curing (21,52). Moreover, ␥␦ T cells are required for the CMI-mediated suppression of P. chabaudi parasitemia in Bcell-deficient mice (49,50,52). The profiles of other splenic mononuclear cells in ␥␦ T-cell-depleted mice (WT and J H Ϫ/Ϫ mice) infected with P. chabaudi did not differ significantly from that of control mice.…”

“…Both cell types have been proposed to play significant roles in the subsequent clearance of blood-stage malarial parasites by activating the adaptive immune system (35,43,44). The mechanism by which they accomplish this appears to be mediated via their secretion of gamma interferon (IFN-␥) induced by cytokines such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-␣), and IL-6 produced by other components of the innate immune system, including macrophages and dendritic cells (17,25,26,37,49).…”

“…Mice depleted of B cells by the same procedures also cure their acute infections in the same timeframe as intact control mice but then develop chronic low-grade parasitemia of long-lasting duration, indicating that B cells and their antibodies are needed to sterilize the infection as we originally reported (15,48) and has since been confirmed by others (51). B-cell-deficient mice depleted of ␥␦ T cells cannot suppress P. chabaudi parasitemia (49,50,52).…”

“…Both responses require CD4 ϩ ␣␤ T cells; in addition, the expression of cellmediated immunity (CMI) during both acute and chronic malaria is dependent on ␥␦ T cells activated by CD4 ϩ ␣␤ T cells (29,47,49,50). Wild-type (WT) mice depleted of ␥␦ T cells by antibody treatment or gene knockout suppress P. chabaudi parasitemia by antibody-mediated immunity (AMI) (21,52).…”

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

“…Conversely, ␥␦ T cells play only a minor role in the control of the acute primary wave of malaria infection, as TCR␥␦ Ϫ/Ϫ or ␥␦ T-cell-depleted mice develop comparable peak parasitemia with little or no delay in parasite clearance (24,43). However, mice deficient in both B cells and ␥␦ T cells develop significantly higher levels of parasitemia, which takes longer to clear, than B-cell or ␥␦ T-cell single deficient animals (46,55), indicative of some redundancy in the protection afforded by these two cell types.…”