Dx: leukemia; Rx: CD8⁺ NKT cell transplantation

Baker and colleagues (page 2923) report that transplantation of the CD8⁺ natural killer T (NKT) lymphocytes results in potent leukemia-specific immunity without causing graft-versus-host disease. Remarkably, transplantation even across major histocompatibility barriers did not induce graft-versus-host response. These virtues of the recently described CD8⁺ NKT cells are their first functional attributes. Bone marrow transplantation (BMT) has emerged as a major therapeutic modality for hematopoietic malignancies. Successful bone marrow engraftment depends on the induction of graftversus-leukemia response to remove (residual) cancer cells while keeping graft-versus-host response in check with an immune suppressive regimen. Because graft-versus-leukemia response is difficult to achieve without triggering graft-versus-host reaction, the potential for BMT as a therapeutic modality has not been fully realized. Previous studies exploring new immunological approaches for successful BMT revealed that NKT lymphocytes, whose immune regulatory function depends on interleukin-4, can suppress graft-versus-host disease. One mechanism by which NKT cells suppress graft-versus-host disease might include the action of the CD8⁺ subset within this immune regulatory T-lymphocyte population.

The findings of Baker and colleagues have important scientific and clinical implications: first, they have developed a method for selective expansion of the CD8⁺ NKT lymphocyte subset ex vivo, which will facilitate studies on how this T-cell subset functions. Second, they report that the leukemia-specific cytolytic function of the CD8⁺ NKT cell subset depends on its ability to secrete interferon γ, which contrasts with the interleukin-4–dependent function of Vα14Jα15⁺ NKT cells. And third, their findings open doors for immune-based therapeutics against blood cell cancers. The anti–cancer cell activity of CD8+ NKT cells could be used for conditioning the recipient prior to BMT. These are exciting times for students of NKT cell biology, as important discoveries await them at the bench holding promise for better patient care at the bedside.