Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response.

Abstract

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for the treatment of leukemia and other immunogenetic disorders. The use of tolerogenic dendritic cells (DCs) that induce the generation/activation of regulatory T (Tr) cells for the treatment of acute GVHD following allogeneic BMT has been recently established. Therefore, the identification of factors that contribute to the development of tolerogenic DCs is highly relevant. We report on the use of the known immunosuppressive neuropeptide, the vasoactive intestinal peptide (VIP), as a new approach to induce tolerogenic DCs with the capacity to prevent acute GVHD. DCs differentiated in the presence of VIP impair allogeneic haplotype-specific responses of donor CD4(+) cells in mice given transplants by inducing the generation of Tr cells in the graft. VIP-induced tolerogenic DCs did not abrogate the graft-versus-leukemia response presumably by not affecting the cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the inclusion of VIP-induced tolerogenic DCs in future therapeutic regimens may minimize the dependence on nonspecific immunosuppressive drugs used currently as antirejection therapy, and facilitate the successful transplantation from mismatched donors, by reducing the deleterious consequences of acute GVHD and extending the applicability of BMT.

• Authors: Alejo Chorny, Elena Gonzalez-Rey, Amelia Fernandez-Martin, Doina Ganea, Mario Delgado
• Journal: Blood (Blood) Vol. 107 Issue 9 Pg. 3787-94 (May 01 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16418327 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Vasoactive Intestinal Peptide

Topics

• Acute Disease
• Animals
• Bone Marrow Transplantation (immunology)
• Dendritic Cells (drug effects, immunology)
• Female
• Graft vs Host Disease (immunology, prevention & control)
• Graft vs Tumor Effect (immunology)
• Immune Tolerance
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• T-Lymphocytes, Regulatory (immunology)
• Transplantation, Homologous
• Vasoactive Intestinal Peptide (pharmacology)