Concurrent allorecognition has a limited impact on posttransplant vaccination

Teresa Manzo, Rodrigo Hess Michelini, Veronica Basso, Alessia Ricupito, Jian Guo Chai, Elizabeth Simpson, Matteo Bellone, Anna Mondino

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1361-1368
Number of pages8
JournalJournal of Immunology
Volume186
Issue number3
DOIs
Publication statusPublished - Feb 1 2011

ASJC Scopus subject areas

  • Immunology

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