Induction of allograft nonresponsiveness after intrathymic inoculation with donor class I allopeptides. II. Evidence for persistent chronic rejection despite high levels of donor microchimerism

Transplantation
H ShirwanD V Cramer

Abstract

We have recently demonstrated that three synthetic peptides corresponding to the donor class I RT1.Aa molecule induce long-term survival of cardiac allografts in the PVG.R8-to-PVG.1U rat strain combination (disparate for one isolated class I, RT1.A, molecule) when presented to the recipient immune system in the thymus. Long-term graft survivors had measurable levels of donor-reactive alloantibodies in their serum. In this study, we examined long-term allografts for the presence of chronic rejection and donor microchimerism to assess whether this regimen of immune modulation establishes true tolerance and whether this tolerance is dependent upon the presence of donor-recipient microchimerism. Histological examination of long-term heart grafts (>100 days) demonstrated chronic rejection, including a mild degree of myocardial infiltration by mononuclear cells, mild to moderate myocardial fibrosis, and various vascular changes ranging from focal intimal thickening to total vascular lumen blockade due to smooth muscle cell proliferation. In contrast, long-term syngeneic hearts transplanted under similar experimental conditions lacked these pathological manifestations. Donor microchimerism was analyzed using the polymerase chain react...Continue Reading

References

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Citations

Mar 16, 2004·Pediatric Diabetes·Rita BottinoMassimo Trucco
May 26, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·K L WomerM H Sayegh
May 20, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Haval ShirwanSherif Ibrahim
Aug 4, 2004·Cell Biochemistry and Biophysics·Soji F OluwoleHector A DePaz
Dec 18, 2009·Expert Review of Molecular Diagnostics·Josep-Maria Pujal
Nov 18, 2003·Immunological Reviews·Maria P Hernandez-FuentesRobert I Lechler
Mar 2, 2011·Current Cardiovascular Imaging Reports·Yijen L WuChien Ho
Jun 27, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·T H StadlbauerM H Sayegh

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