期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 17, 期 6, 页码 790-799出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2010.12.712
关键词
Allogeneic bone marrow transplantation; Donor lymphocyte infusion; Immune reconstitution; Vaccine
资金
- National Institutes of Health
- Children's Cancer Foundation
- Lisa's Heart Kids Cancer Research Fund
Extracorporeal photopheresis (ECP) is emerging as a therapy for graft-versus-host-disease (GVHD), but the full mechanism of action and the impact on immunity have not been fully established. After murine minor histocompatibility antigen-mismatched bone marrow (BM) transplantation (allo-BMT), coinfusion of ECP-treated splenocytes with T cell-replete BM attenuated GVHD irrespective of the donor strain of the ECP-treated splenocytes, and was associated with increased numbers of regulatory T cells. Coculture of myeloid dendritic cells (DCs) with ECP-treated splenocytes resulted in increased interleukin (IL)-10 production after submaximal stimulation with lipopolysaccharide. Furthermore, male myeloid DCs exposed to ECP-treated splenocytes were less potent at inducing CD8(+) HY responses when used as a vaccine in vivo. The efficacy of ECP-treated splenocytes was enhanced when administered just before delayed donor lymphocyte infusion following T cell-depleted allo-BMT, allowing for the administration of sufficient numbers of T cells to respond to myeloid DC vaccination in the absence of a thymus. Finally, the therapeutic effect of ECP-treated splenocytes was lost in recipients of IL-10 deficient BM. We demonstrate that ECP-treated splenocytes attenuate GVHD irrespective of the source of ECP-treated cells via a mechanism that likely involves modulation of DCs and requires IL-10 produced by BM-derived cells. Importantly, the attenuation of GVHD by ECP-treated splenocytes permits donor lymphocyte infusion dependent responses to DC vaccines after allo-BMT. Biol Blood Marrow Transplant 17: 790-799 (2011) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation
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