Th2 cell therapy of established acute graft-versus-host disease requires IL-4 and IL-10 and is abrogated by IL-2 or host-type antigen-presenting cells.

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Jason E FoleyDaniel H Fowler

Abstract

Delayed donor Th2 cell infusion permits a graft-versus-tumor (GVT) effect to occur with subsequent amelioration of established graft-versus-host disease (GVHD). Relative to GVHD controls (B6-into-BALB/c model), recipients of delayed Th2 cells (day 14 post-BMT) had increased survival (3/3 experiments [exp]; each exp P < .0001) and reduced GVHD by histology analysis 5 days post-Th2 infusion without increased tumor burden (3 of 3 exp; each exp P < or = .02). Th2 cell-mediated amelioration of GVHD was associated with greatly reduced allospecific IFN-gamma secretion, in vivo augmentation of allospecific IL-4 and IL-10 secretion, and reduction in donor CD8(+) T cell number post-BMT (3 of 3 exp; each comparison, P < or = .003). To better understand the molecular mechanism of this GVHD therapy, Th2 cells were generated from wild-type (WT), IL-4 deficient (KO), or IL-10 KO donors: remarkably, recipients of IL-4 or IL-10 KO Th2 cells had no survival advantage, no improvement in GVHD by histology, no reduction in CD8(+) T cell expansion post-BMT, and no in vivo shift toward type II cytokines. We reasoned that IL-2 and alloantigen availability may be limiting factors for Th2 cell therapy, and as such, evaluated whether coadministration of ...Continue Reading

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Citations

Oct 3, 2009·Blood·Daniel Fowler
Jul 15, 2011·Immunotherapy·Takanori TeshimaKatsutoshi Ozaki
Jun 4, 2013·Immunotherapy·Massimo MartinoFortunato Morabito
Jun 6, 2013·Biomarkers in Medicine·Bei Ge, Haige Ye
Feb 26, 2014·Bone Marrow Transplantation·Y-J Chang, X-J Huang
Apr 5, 2014·Archivum Immunologiae Et Therapiae Experimentalis·Jianing FuXue-Zhong Yu
Sep 10, 2014·Expert Review of Clinical Immunology·Perla Filippini, Sergio Rutella
May 22, 2009·Expert Opinion on Biological Therapy·Matthew D ScaifeJ A Medin
May 14, 2011·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K L HippenB R Blazar
Dec 18, 2013·Immunological Reviews·Daniel H Fowler
May 21, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Holbrook E KohrtRobert Lowsky
Oct 30, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mehdi HamadaniMichael D Craig
May 4, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nina C ZitzerParvathi Ranganathan
Jun 14, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Miriam E MossobaDaniel H Fowler
Apr 1, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Charles S ViaFred D Finkelman

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