CD1d‐restricted NKT cells contribute to malarial splenomegaly and enhance parasite‐specific antibody responses

Abstract

CD1d‐restricted NKT cells are a novel T cell lineage with unusual features. They co‐express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN‐γ and IL‐4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d‐restricted NKT cell activation in the induction of B cell‐mediated immune responses to infection is still unclear. We show here that CD1‐restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite‐specific antibody formation in response to Plasmodium berghei infection. The increased B cell‐mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)‐anchored protein merozoite surface protein 1 (MSP‐1) were found to be significantly lower in CD1^–/– mice compared to wild‐type animals. P. berghei‐infected MHC class II (MHCII)^–/– mice also generated antibodies against MSP‐1, suggesting that antibody production against GPI‐anchored antigens in response to malaria infection can arisefrom both MHCII‐dependent and independent pathways.