title: Concurrent allorecognition has a limited impact on posttransplant vaccination.
abstract: 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.
authors.affiliation: Program in Immunology and Bio-Immuno-gene therapy of Cancer, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Manzo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Hess Michelini
authors.forename: Veronica
authors.initials: V
authors.lastname: Basso
authors.forename: Alessia
authors.initials: A
authors.lastname: Ricupito
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chai
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Simpson
authors.forename: Matteo
authors.initials: M
authors.lastname: Bellone
authors.forename: Anna
authors.initials: A
authors.lastname: Mondino
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006182:H-Y Antigen / Q000008:administration & dosage / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000008:administration & dosage* / Q000276:immunology; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma