C-kit-derived CD11b+ cells are critical for cardiac allograft prolongation by autologous C-kit+ progenitor cells

C-kit-derived CD11b+ cells are critical for cardiac allograft prolongation by autologous C-kit+ progenitor cells

•Autologous bone marrow-derived C-kit+ cells prolong murine cardiac allografts.•Alloimmunity may be critical for influx of C-kit+ cells into cardiac allografts.•A majority of C-kit-derived cells differentiate to CD11b+ cells in the allograft.•Allograft prolongation requires CD11b+ cells from the C-k...

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Published in:Cellular immunology Vol. 347; p. 104023
Main Authors: Plenter, R.J., Coulombe, M.G., Roybal, H.M., Lin, C.M., Gill, R.G., Zamora, M.R., Grazia, T.J.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 01-01-2020
Subjects:
Allograft prolongation
Cardiac transplantation
CD11b
Cell therapy
Ckit
Progenitor cell
IFNγ
DT
PC
Cell therapy
Ckit
Allograft prolongation
Cardiac transplantation
MLN
SPL
CD11b
DC
Progenitor cell
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Summary:•Autologous bone marrow-derived C-kit+ cells prolong murine cardiac allografts.•Alloimmunity may be critical for influx of C-kit+ cells into cardiac allografts.•A majority of C-kit-derived cells differentiate to CD11b+ cells in the allograft.•Allograft prolongation requires CD11b+ cells from the C-kit+ donor cell pool.•Addition of Cyclosporine or CTLA4Ig is not detrimental to allograft prolongation. Autologous C-kit+ cells robustly prolong cardiac allografts. As C-kit+ cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit+ cells were administered post-cardiac transplantation and allografts were evaluated for C-kit+ inoculum-derived cells. Results suggested that alloimmunity was a major signal for trafficking of C-kit-derived cells to the allograft and demonstrated that C-kit+ inoculum-derived cells expressed CD11b early after transfer. Allograft survival studies with CD11b-DTR C-kit+ cells demonstrated a requirement for C-kit+-derived CD11b+ cells. Co-therapy studies demonstrated near complete abrogation of acute rejection with concomitant CTLA4-Ig therapy and no loss of prolongation in combination with Cyclosporine A. These results strongly implicate a C-kit-derived myeloid population as critical for allograft preservation and demonstrate the potential therapeutic application of autologous C-kit+ progenitor cells as calcineurin inhibitor-sparing agents and possibly as co-therapeutics for durable graft survival.
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ISSN:0008-8749
1090-2163
1090-2163
DOI:10.1016/j.cellimm.2019.104023