Blood, 15 May 2001, Vol. 97, No. 10, pp. 2921-2922
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 
, which contrasts with the
interleukin-4-dependent function of V
14J15+ 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.
Sebastian Joyce
Vanderbilt University School of Medicine
