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(Journal of Leukocyte Biology. 2002;72:898-912.)
© 2002 by Society for Leukocyte Biology

Donor T cell and host NK depletion improve the therapeutic efficacy of allogeneic bone marrow cell reconstitution in the nonmyeloablatively conditioned tumor-bearing host

Susanne Hummel*, Daniela Wilms*, Mario Vitacolonna* and Margot Zöller*,{dagger}

* Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg; and
{dagger} Department of Applied Genetics, University of Karlsruhe, Germany

Correspondence: Margot Zöller, Department of Tumor Progression and Immune Defense, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. E-mail: m.zoeller{at}dkfz.de

Allogeneic bone marrow cell reconstitution of the nonmyeloablatively conditioned host has the advantage that it can be tolerated in suboptimal health conditions. However, the problem of graft versus host disease (GvHD) remains. Also, graft acceptance may become delicate, and HvGD may arise. We report here on advantages/disadvantages of host natural killer (NK) depletion and graft T cell depletion in fully allogeneic, healthy and solid tumor-bearing mice. NK depletion of the "healthy" host improved the survival rate, whereas graft T cell depletion was disadvantageous. In the tumor-bearing host, graft T cell depletion was beneficial when the host was NK-depleted. Host NK depletion facilitated B lymphopoiesis, repopulation of the thymus, expansion of donor cells, and tolerance induction. The disadvantage of graft T cell depletion in the "healthy" host was a result of delayed engraftment. Because in tumor-bearing mice, host but not graft hematopoiesis was strongly impaired, donor hematopoiesis dominated. Graft T cell depletion reduced GvHD but hardly interfered with engraftment. Importantly, graft-mediated tumor reactivity appeared late and was unimpaired when the graft was T cell-depleted. Thus, concomitant depletion of host NK and donor T cells is advantageous when approaching therapeutic treatment of solid tumors by allogeneic reconstitution of the nonmyeloablatively conditioned host.

Key Words: rodent • graft versus host disease • transplantation • carcinoma




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