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

Paul C. Grimm, Peter Nickerson, John Jeffery, Rashmin C. Savani, James Gough, Rachel M. McKenna, Elzbieta Stern, David N. Rush

Research output: Contribution to journalArticle

235 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalNew England Journal of Medicine
Volume345
Issue number2
DOIs
StatePublished - Jul 12 2001

ASJC Scopus subject areas

  • Medicine(all)

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