Rapid tolerance induction by hematopoietic progenitor cells in the absence of donor-matched lymphoid cells. Transpl Immunol 2014 Aug;31(2):112-8
Date
05/06/2014Pubmed ID
24794050DOI
10.1016/j.trim.2014.04.001Scopus ID
2-s2.0-84906054966 (requires institutional sign-in at Scopus site) 1 CitationAbstract
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.
Author List
Domen J, Li Y, Sun L, Simpson P, Gandy KAuthor
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDNA-Binding Proteins
Donor Selection
Forkhead Transcription Factors
Graft Survival
Hematopoietic Stem Cell Transplantation
Interleukin Receptor Common gamma Subunit
Mice
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Myeloid Progenitor Cells
Skin Transplantation
T-Lymphocytes, Regulatory
Transplantation Tolerance
Transplantation, Homologous