Invariant NKT cells are required for antitumor responses induced by host-versus-graft responses.
Based on clinical observations, we have previously shown in a murine model that recipient leukocyte infusion (RLI) induces a host-versus-graft reaction in mixed bone marrow chimeras and that rejection of donor cells leads to a specific antitumor response against recipient malignancies. This response is dependent on T cells and IFN-gamma. We investigated the role of NKT cells (NKTs) in this phenomenon. Depletion of recipient NK1.1(+) cells led to loss of an anti-tumor effect induced by RLI in mixed bone marrow chimeras. In recipients specifically lacking host invariant NKT cells (iNKTs), RLI did not induce an antitumor effect, indicating a critical role for recipient iNKTs. Conversely, specific activation of iNKTs enhanced the anti-tumor effect induced by RLI. Following RLI, recipient iNKTs, NK cells, dendritic cells (DCs), and CD8 T cells were activated. CD8 T cells were the major producers of IFN-gamma. Lack of recipient iNKTs resulted in failure of activation of NK cells and DCs by RLI. Our studies demonstrate a central role for iNKTs in promoting RLI-induced anti-tumor effects and suggest that this pathway involved promotion of the activation of recipient NK cells and DCs.
Saito
Toshiki I
TI
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Li
Hao Wei
HW
Sykes
Megan
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006789:Host vs Graft Reaction / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D017708:Leukocyte Transfusion; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera / Q000097:blood / Q000276:immunology
D015847:Interleukin-4; D007371:Interferon-gamma