Rapid tolerance induction by hematopoietic progenitor cells in the absence of donor-matched lymphoid cells

• Published in: Transplant immunology 2014-08, Vol.31 (2), p.112-118
• Main Authors: Domen, Jos, Li, Yongwu, Sun, Lei, Simpson, Pippa, Gandy, Kimberly
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; DNA-Binding Proteins - genetics; Donor Selection; Forkhead Transcription Factors - genetics; Graft Survival - immunology; Hematopoietic stem cell; Hematopoietic Stem Cell Transplantation; Interleukin Receptor Common gamma Subunit - genetics; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Myeloid progenitor; Myeloid Progenitor Cells - immunology; Myeloid Progenitor Cells - transplantation; Rodent; Skin Transplantation - methods; T-Lymphocytes, Regulatory - immunology; Tolerance; Transplantation; Transplantation Tolerance - immunology; Transplantation, Homologous
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2014.04.001

Abstract Background Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific tolerance for subsequently transplanted organs [1]. Methods Mice received an allogeneic HSC and third party MP transplantation simultaneous with placement of a MP-matched skin graft. Variants tested include time of graft placement, MP genotype and source of cells. Results Using B10;B6-Rag2−/− Il2rg−/− mice, we demonstrate that specific tolerance can be induced by MP given simultaneous with the skin graft in the complete absence of MP-donor-matched lymphoid cells. Ex vivo expanded MP function as well as sorted cells in inducing tolerance. In addition we demonstrate that tolerance can be induced by MP in the context of autologous HSC transplantation. Conclusions Our results demonstrate that the previously observed expansion of organ donor matched Treg is not essential for tolerance, and that MP tolerance protocols can be envisioned in most clinical settings, including those involving deceased donor organs.