Transplantation of allogeneic hematopoietic stem cells with or without immunocompetent lymphocytes has proved a successful strategy in the treatment of
hematological malignancies. We have recently shown that this approach can also cure mouse
prostate cancer, provided that it is combined with
tumor-specific vaccination. Whether the response to
alloantigens acts by providing helper function to enhance
vaccine-specific responses or in other ways impinges on vaccine immunogenicity remains to be clarified, and this question is of clinical relevance. In this study, we have addressed this issue by comparing the immunogenicity of dendritic cells pulsed with a
peptide derived from a
tumor/viral model Ag in recipients of donor cells either syngeneic to the host or differing for either Y-encoded or multiple minor H
antigens. We report that vaccination elicits comparable proliferation and differentiation of
peptide-specific CD8(+) T cells despite concurrent expansion and differentiation of minor
H antigen-specific IFN-γ effector T cells. Depletion of alloreactive CD4(+) T cells reduced alloreactivity but not
vaccine-induced CD8(+) T cell priming, suggesting that alloresponses do not provide helper functions in peripheral lymphoid tissues.
Vaccine-mediated T cell priming was also preserved in the case of multiple minor
H antigen disparities, prone to
graft-versus-host disease. Thus, in the context of nonmyeloablative allotransplantation aimed at restoring an effective
tumor-specific T cell repertoire, minor
H antigen-specific T cells do not interfere with
vaccine-induced T cell priming, supporting the notion that posttransplant vaccination is a valuable strategy to boost
tumor and pathogen-specific protective immunity.