Allorecognition and effector pathways of islet allograft rejection in normal versus nonobese diabetic mice

Leila Makhlouf, Akira Yamada, Toshiro Ito, Reza Abdi, Mohammed Javeed I Ansari, Chau Q. Khuong, Henry J. Winn, Hugh Auchincloss, Mohamed H. Sayegh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Islet transplantation is becoming an accepted therapy to cure type I diabetes mellitus. The exact mechanisms of islet allograft rejection remain unclear, however. In vivo CD4+ and CD8+ T cell-depleting strategies and genetically altered mice that did not express MHC class I or class II antigens were used to study the allorecognition and effector pathways of islet allograft rejection in different strains of mice, including autoimmunity-prone nonobese diabetic (NOD) mice. In BALB/c mice, islet rejection depended on both CD4+ and CD8+ T cells. In C57BL/6 mice, CD8+ T cells could eventually mediate islet rejection by themselves, but they produced rejection more efficiently with help from CD4+ T cells stimulated through either the director indirect pathway. In C57BL/6 mice, CD4+ T cells alone caused islet rejection when only the direct pathway was available but not when only the indirect pathway was available. In contrast, in NOD mice, CD4+ T cells alone, with only the indirect pathway, could mediate islet and cardiac allograft rejection. These findings indicate that different mouse strains can make use of different pathways for T cell-mediated rejection of islet allografts. In addition, they demonstrate that NOD mice, which develop autoimmunity and are known to be resistant to tolerance induction, have an unusually powerful CD4+ cell indirect mechanism that can cause rejection of both islet and cardiac allografts. These data shed light on the mechanisms of islet allograft rejection in different responder strains, including those with autoimmunity.

Original languageEnglish (US)
Pages (from-to)2168-2175
Number of pages8
JournalJournal of the American Society of Nephrology
Issue number8
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Medicine(all)


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