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

Mouse natural killer T cells with an invariant V alpha 14-J alpha 18 TCR rearrangement (V alpha 14i 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 Va14i NKT cell ligand, a-galactosylceramide (alpha-Ga1Cer) 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 Va14i NKT cells using a-GalCer and IL-2 could modulate acute GVHD in the transplantation of spleen cells of C57BL/6 mice into (B6 x DBA/2) F-1 mice. We found that the adoptive transfer of cultured spleen cells with a combination of alpha-GalCer and IL-2, which contained many V alpha 14i NKT cells, modulated acute GVHD by exhibiting long-term mixed chimerism and reducing liver damage. Subsequently, the transfer of V alpha 14i NKT cells purified from spleen cells cultured with a-Ga1Cer and IL-2 also inhibited acute GVHD. This inhibition of acute GVHD by V alpha 14i NKT cells was blocked by anti-IL-4 but not by anti-IFN-gamma monoclonal antibody. Therefore, the inhibition was dependent on IL-4 production by V alpha 14i NKT cells. Our findings highlight the therapeutic potential of in vitro-expanded V alpha 14i NKT cells for the prevention of acute GVHD after allogeneic hematopoietic stem cell transplantation. (c) 2006 Elsevier B.V All rights reserved.