[HTML][HTML] Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection

PC Grimm, P Nickerson, J Jeffery… - … England Journal of …, 2001 - Mass Medical Soc
PC Grimm, P Nickerson, J Jeffery, RC Savani, J Gough, RM McKenna, E Stern, DN Rush
New England Journal of Medicine, 2001Mass Medical Soc
Background Tissue remodeling depends on mesenchymal cells (fibroblasts and
myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not
known whether the mesenchymal cells that participate in remodeling originate locally or
from circulating precursor cells. Methods We obtained biopsy specimens of renal allografts
from six male recipients of an allograft from a female donor, four female recipients of an
allograft from a male donor, two male recipients of an allograft from a male donor, and two …
Background
Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells.
Methods
We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle α-actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA.
Results
No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (±SD) of 34±16 percent of mesenchymal cells in the neointima, 38±12 percent of such cells in the adventitia, and 30±7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24±15 percent, 33±9 percent, and 23±8 percent, indicating a persistent population of donor mesenchymal cells.
Conclusions
The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation.
The New England Journal Of Medicine