Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Vα14 natural killer T cells

Abstract

Mouse natural killer T cells with an invariant Vα14-Jα18 TCR rearrangement (Vα14i NKT cells) are able to regulate immune responses through rapid and large amounts of Th1 and Th2 cytokine production. It has been reported that in vivo administration of the Vα14i NKT cell ligand, α-galactosylceramide (α-GalCer) significantly reduced morbidity and mortality of acute graft-versus-host disease (GVHD) in mice. In this study, we examined whether adoptive transfer of in vitro-expanded Vα14i NKT cells using α-GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells of C57BL/6 mice into (B6 × DBA/2) F 1 mice. We found that the adoptive transfer of cultured spleen cells with a combination of α-GalCer and IL-2, which contained many Vα14i NKT cells, modulated acute GVHD by exhibiting long-term mixed chimerism and reducing liver damage. Subsequently, the transfer of Vα14i NKT cells purified from spleen cells cultured with α-GalCer and IL-2 also inhibited acute GVHD. This inhibition of acute GVHD by Vα14i NKT cells was blocked by anti-IL-4 but not by anti-IFN-γ monoclonal antibody. Therefore, the inhibition was dependent on IL-4 production by Vα14i NKT cells. Our findings highlight the therapeutic potential of in vitro-expanded Vα14i NKT cells for the prevention of acute GVHD after allogeneic hematopoietic stem cell transplantation.