Blood, 15 April 2001, Vol. 97, No. 8, pp. 2193-2194
A time to live, a time to die
T cells contained in marrow or mobilized peripheral blood
apheresis products used for hematopoietic stem cell transplantation have both beneficial and detrimental effects in allogeneic recipients. Donor T cells that recognize recipient alloantigens prevent rejection and recurrent malignancy but also cause graft-versus-host disease (GVHD). Donor T cells that do not recognize recipient alloantigens contribute to immune reconstitution after the transplantation. The
"surgical" approach of removing all T cells in the graft prevents GVHD but also prevents the beneficial effects of these cells. Drobyski
and colleagues (page 2506) have identified a way to retain some of the
benefits of donor T cells while preventing GVHD.
Previous studies have shown that GVHD can easily be prevented when
donor T cells are transfected to express the H simplex virus
enzyme thymidine kinase. Proliferating cells that express this enzyme
are susceptible to ganciclovir, an antiviral drug. When ganciclovir is
given at the right time after transplantation, TK+ donor T
cells that proliferate rapidly in response to recipient alloantigens
are induced to commit suicide, while some of the more slowly
proliferating cells that do not recognize recipient alloantigens are
spared. Drobyski and colleagues now show for the first time that, by
delaying the administration of ganciclovir until 8-12 days after the
transplantation, donor T cells that recognize recipient alloantigens
have enough time to prevent rejection but not enough time to cause
severe GVHD. These results offer proof of principle that strategies can
be developed for controlling the detrimental effects of donor T cells
while retaining some of their benefits. Precise balance in the
conditioning regimen, number of T cells, and timing of ganciclovir
administration was needed for success with this approach, emphasizing
the formidable complexity likely to be encountered when attempts are
made to translate these results in hematopoietic stem cell
transplantation for humans.
Paul Martin
Fred Hutchinson Cancer Research Center
