On histocompatibility barriers, Th1 to Th2 immune deviation, and the nature of the allograft responses

Xian Chang Li, Martin S. Zand, Yongsheng Li, Xin Xiao Zheng, Terry B. Strom

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

In the present study, we have sought to determine the basis for the frequent failure of Th1 to Th2 immune deviation to blunt the severity of allograft rejection, as such immune deviation has proven highly effective in the treatment of several T cell-dependent autoimmune states. Our study demonstrates that treating islet allograft recipient mice with anti-IL-12 mAb is highly effective in producing Th1 to Th2 immune deviation in several model systems (i.e., fully MHC, partially MHC, or multiple minor Ag barriers). Nevertheless, anti-IL-12 failed to prolong the engraftment of fully MHC- mismatched islet allografts. However, anti-IL-12-treated recipients carrying MHC-matched but multiple minor Ag-mismatched allografts experienced prolonged engraftment; allograft tolerance was frequently achieved in the DBA/2J (H- 2(d)) to BALB/c (H-2(d)) strain combination. In another model, in which the host response was dominated by CD4+ T cells responding to donor allopeptides presented upon host APCs in the context of self MHC class H molecules, anti- IL-12 treatment proved to be extremely potent. Thus, Th1 to Th2 immune deviation produces prolonged engraftment as compared with recipients of MHC- mismatched allografts when rejection is dependent upon indirectly presented allogeneic peptides and a reduced mass of responding alloreactive T cells.

Original languageEnglish (US)
Pages (from-to)2241-2247
Number of pages7
JournalJournal of Immunology
Volume161
Issue number5
StatePublished - Sep 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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