Th1 to Th2 immune deviation facilitates, but does not cause, islet allograft tolerance in mice.


Journal Article

It has been reported that Th1 to Th2 immune deviation effectively promotes peripheral tolerance in situations involving a limited T cell clone size, such as T cell-dependent autoimmunity and transplantation across minor, but not major, histocompatibility barriers. In this study, we tested the hypothesis that while Th1 to Th2 immune deviation fails to induce tolerance in the MHC-mismatched islet allograft model, it may promote a state that is permissive for tolerance induction. Here, we report that anti-IL-12 did not prevent acute rejection of islet allografts when administered alone. In conjunction with CTLA4/Fc, however, anti-IL-12 greatly facilitated long-term engraftment in three MHC-mismatched strain combinations. Similarly, while non-cytolytic IL-4/Fc, a long-lasting form of IL-4, did not prevent acute graft rejection when administered alone, a low, but not a high, dose of IL-4/Fc synergized with CTLA4/Fc in inducing significant levels of islet allograft tolerance. Moreover, by using a skin allograft adoptive transfer model, we show that these effects induced by anti-IL-12 and IL-4/Fc treatment were associated with an enhancement of the suppressive properties of CD4(+)CD25(+) regulatory T cells. Thus, anti-IL-12 and low-dose IL-4/Fc facilitate, but do not cause, islet allograft tolerance in mice by increasing the immunosuppressive potency of CD4(+)CD25(+) regulatory T cells.

Full Text

Cited Authors

  • Zhang, D; Sanchez-Fueyo, A; Kawamoto, K; Alexopoulos, SP; Zhang, W; Zheng, XX

Published Date

  • September 2010

Published In

Volume / Issue

  • 51 / 3

Start / End Page

  • 311 - 319

PubMed ID

  • 20598563

Pubmed Central ID

  • 20598563

Electronic International Standard Serial Number (EISSN)

  • 1096-0023

International Standard Serial Number (ISSN)

  • 1043-4666

Digital Object Identifier (DOI)

  • 10.1016/j.cyto.2010.06.007


  • eng