Abstract
Invariant natural killer T (iNKT) cells are a major subset of NKT cells that recognize foreign and endogenous lipid antigens presented by CD1d. Although iNKT cells are characteristically autoreactive to self-antigens, the role of iNKT cells in the regulation of cytotoxic T lymphocytes (CTL) has been elucidated using α-galactosylceramide (α-GalCer), a strong synthetic glycolipid that is presented by professional antigen presenting cells (APCs), such as dendritic cells. Despite the well-known effects of α-GalCer and dendritic cells on lipid antigen presentation, the physiological role of endogenous antigens presented by CTLs during crosstalk with iNKT cells has not yet been addressed. In this study, we found that antigen-primed CTLs with transient CD1d upregulation could present lipid self-antigens to activate the iNKT cell production of IFN-γ. CTL-mediated iNKT cell activation in turn enhanced IFN-γ production and the proliferation and cytotoxicity of CTLs. We also found that the direct interaction of iNKT cells and CTLs enhanced the antitumor immune responses of CTLs. This partially explains the functional role of iNKT cells in CTL-mediated antitumor immunity. Our findings suggest that in the absence of exogenous iNKT cell ligands, iNKT cells enhanced the CTL production of IFN-γ and CTL proliferation and cytotoxicity via direct interaction with CD1d expressed on T cells without interacting with APCs.
Highlights
Introduction Natural killerT (NKT) cells are a subset of TCR αβ cells that recognize self and foreign lipids and glycolipid antigens presented by the MHC class I-like molecule CD1d
dendritic cells (DCs) and exogenous Natural killerT (NKT) cell agonizts First, we examined whether Invariant NKT (iNKT) cells directly promoted CD8+ T-cell activation or if CD8+ T cells were
We investigated whether OT-1 CD8+ T cells could activate iNKT cells via endogenous antigens presented on CD1d. iNKT cells were cocultured with CD1dWT OT-1 or CD1d knockout mice (CD1dKO) OT-1 cells
Summary
Introduction Natural killerT (NKT) cells are a subset of TCR αβ cells that recognize self and foreign lipids and glycolipid antigens presented by the MHC class I-like molecule CD1d. Many reports have suggested that the activation of iNKT cells enhances the CTL-mediated elimination of cancer cells or various infections[9,10,11,12] Most of these studies were focused on the activation of iNKT cells following stimulation with foreign glycolipids, such as the marine sponge-derived glycolipid α-galactosylceramide (α-GalCer), a strong and prototypical synthetic glycolipid[9,10,13,14,15]. In these immune responses, activated iNKT cells potentiate dendritic cells (DCs) in a CD40-
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