Mature donor-derived T cells in allogeneic bone marrow (BM) transplants mediate the graft-versus-
tumor (GVT) effect by recognizing
alloantigens on leukemic cells. However,
alloantigen reactivity towards non-malignant tissues also induces
graft-versus-host disease (GVHD). Defining T-cell subpopulations that mediate the GVT effect in the absence of GVHD induction remains a major challenge in allogeneic BM
transplantation. In this study, we show that in vitro-generated
alloantigen-specific CD8(+) cytotoxic T cells (CTLs) established by weekly stimulation with
alloantigen-expressing antigen-presenting cells did not induce GVHD in two major histocompatibility complex-mismatched BM
transplantation models, where induction of lethal GVHD is dependent on the presence of either CD4(+) or CD8(+) T cells. Despite their strong
alloantigen specificity,
transplantation of CTLs did not induce the expression of GVHD-associated
cytokines IFN-γ and TNF-α or clinical or histological signs of GVHD, and lead to a survival rate of above 90%. However,
transplantation of unstimulated CD8(+) T cells, which were not primed by the
alloantigen in vitro, induced GVHD in both the
transplantation models. Although CTLs were impaired in GVHD induction, they efficiently eradicated Bcr-Abl-transformed
B-cell leukemias or mastocytomas. Thus, in vitro-derived CTLs might be useful for optimizing anti-
tumor therapy in the absence of GVHD induction.