Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides

Nepal C. Chowdhury, Barbara Murphy, Mohamed H. Sayegh, Ming Xing Jin, Dilip K. Roy, Mark A. Hardy, Soji F. Oluwole

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

This study extends the finding that intrathymic (IT) injection of 3M KCl extracts of T cells induces transplant tolerance to the use of well defined polymorphic MHC class I allopeptides derived from the hypervariable domain of RT1.A(u) (WF MHC class I). While three of the six synthetic RT1.A(u) peptides were immunogenic, three others were nonimmunogenic when tested in ACI responders. In our initial studies, we examined the effects of IT injection of a mixture of equal concentrations of the three nonimmunogenic RT1.A(u) peptides on WF cardiac allograft survival in ACI recipients. The results showed that a single IT injection of 100 and 300 μg class I MHC allopeptides on day -7 relative to cardiac transplant did not significantly prolong graft survival in naive ACI recipients (MST of 9.8, and 12.3 days vs. 10.5 days in controls). In contrast, 600 mg allopeptides injected IT resulted in modest prolongation of graft to an MST of 19.5 days. However, IT injection of 600 μg allopeptides combined with 0.5 ml ALS on day -7 led to permanent acceptance (>200 days) of cardiac allografts in 7/9 ACI recipients compared with survival of 24.2 days in ALS alone treated controls. In contrast, similar treatment led to acute rejection of third party (Lewis) cardiac allografts. Intravenous injection of 600 μg allopeptides combined with ALS did not result in prolonged graft survival (26.8 days). The long-term unresponsive ACI recipients (> 100 days) challenged with second-set cardiac grafts accepted permanently donor-type (WF) grafts while rejecting the third party (Lewis) grafts, a finding that confirms acquired systemic tolerance. These findings confirm the role of IT injection of synthetic polymorphic allopeptides in the induction of acquired thymic tolerance and provide the rationale for testing this strategy in large animals and eventually in man.

Original languageEnglish
Pages (from-to)1878-1882
Number of pages5
JournalTransplantation
Volume62
Issue number12
DOIs
StatePublished - 27 Dec 1996

Fingerprint

Dive into the research topics of 'Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides'. Together they form a unique fingerprint.

Cite this