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ABSTRACT
For over 50 y the association between hematopoietic chimerism and tolerance has been recognized. This originated with the brilliant observation by Dr. Ray Owen that freemartin cattle twins that shared a common placental blood supply were red blood cell chimeras, which led to the discovery that hematopoietic chimerism resulted in actively acquired tolerance. This was first confirmed in neonatal mice by Medawar et al. and subsequently in adult rodents. Fifty years later this concept has been successfully translated to solid organ transplant recipients in the clinic. The field is new, but cell-based therapies are being used with increasing frequency to induce tolerance and immunomodulation. The future is bright. This review focuses on chimerism and tolerance: past, present and prospects for the future.
Abbreviations
| DSA | = | donor specific antibody |
| DSH | = | donor specific hyporesponsiveness |
| FC | = | facilitating cells |
| FCRx | = | a tolerance-promoting facilitating cell-based hematopoietic stem and progenitor cell graft |
| GVHD | = | graft versus host disease |
| HPC | = | hematopoietic progenitor cells |
| HSC | = | hematopoietic stem cells |
| HSCT | = | hematopoietic stem cell transplantation |
| MHC | = | major histocompatibility complex |
| NSG | = | NOD scid gamma |
| ODN | = | oligodeoxynucleotide |
| PRA | = | panel reactive antibody |
| pre-pDC | = | precursor-plasmacytoid dendritic cells |
| TREC | = | T-cell receptor excision circle |
Disclosure of potential conflicts of interest
Dr. Suzanne Ildstad has equity interest in Regenerex, LLC, a start-up biotech company. In 2013, the company entered into a global licensing and research collaboration agreement with Novartis for the development of FCRx.
Acknowledgments
The authors thank Kimberly Nichols and Marilyn McLendon for manuscript preparation and Dr. Andreas Katopodis at Novartis Institutes for Biomedical Research for manuscript review.