NK T cells promote IL-21 secretion and enhance Ab production and affinity maturation during Plasmodium yoelii infection

Abstract

Abstract NK T cells are a class of lipid antigen-restricted CD4+ T cell possessing qualities of both innate and adaptive immune cells. In addition to rapid production of various effector cytokines, NK T cells have also been shown to play a role in modulating the germinal center (GC) reaction directly by differentiation into NK-Tfh cells, or indirectly by promoting dendritic cell (DC) maturation. Due to their ability to enhance DC expression of MHCII and B7-family co-stimulatory molecules, synthetic glycolipids that target NK T cells are being considered as adjuvants in a number of vaccine approaches designed to facilitate conventional CD4+ T cell activation. During Plasmodium infection, a pathogen for which a vaccine is greatly needed, NK T cells have been shown to be responsive to parasite-derived glycolypids. To assess the contribution of NK T cells to the GC reaction following Plasmodium infection, NK T cells were depleted during murine Plasmodium yoelii infection. Here, we demonstrate that NK T cell depletion did not result in the production of fewer conventional Tfh cells or GC B cells. However, depletion of NK T cells resulted in decreased frequency and total number of IL-21–producing CD4+ T cells. This resulted in NK T cell depleted mice producing a lower quantity and quality of MSP-119-specific IgG Abs when compared to control mice. Ultimately, the decrease in Ab titer was attributed to significantly fewer MSP-119-specific IgG antibody-secreting cells in the bone marrow of NK T cell depleted mice. Collectively, this data suggests NK T cells play an important role in shaping the GC reaction during P. yoelii infection. Successful modulation of NK T cell activity could prove a useful strategy in future Plasmodium vaccine design.