Interferon-γ is not a universal requirement for islet allograft survival1

MR Nicolls, M Coulombe, AS Diamond, J Beilke… - …, 2002 - journals.lww.com
MR Nicolls, M Coulombe, AS Diamond, J Beilke, RG Gill
Transplantation, 2002journals.lww.com
Background. Although many transplantation studies have implicated a graft-destructive role
for T helper (Th) 1 cytokines and a graft-protective role for Th2 cytokines, more recent
studies have challenged this paradigm by showing that long-term allograft survival can
actually require the presence of Th1 cytokines, such as interleukin 2 and interferon (IFN)-γ.
The purpose of this study was to examine the requirement for IFN-γ in the induction of islet
allograft acceptance after monoclonal antibody therapy targeting conceptually distinct …
Abstract
Background.
Although many transplantation studies have implicated a graft-destructive role for T helper (Th) 1 cytokines and a graft-protective role for Th2 cytokines, more recent studies have challenged this paradigm by showing that long-term allograft survival can actually require the presence of Th1 cytokines, such as interleukin 2 and interferon (IFN)-γ. The purpose of this study was to examine the requirement for IFN-γ in the induction of islet allograft acceptance after monoclonal antibody therapy targeting conceptually distinct molecular pathways: the costimulatory molecule CD154, the CD4 coreceptor, or the β2 integrin lymphocyte function-associated antigen (LFA)-1 (CD11a).
Methods.
Diabetic C57Bl/6 (B6; H2 b) mice were grafted with fully MHC mismatched BALB/c (H2 d) islets, or reciprocally, diabetic BALB/c mice underwent transplantation with B6 islets and were treated with anti-CD154, anti-CD4, or anti-LFA-1.
Results.
When IFN-γ gene knockout mice were used as graft recipients, the requirement for IFN-γ in allograft survival was found to be highly conditional, depending on both the host strain and the induction therapy used. In both strain combinations studied, anti-CD154 was effective in the presence or absence of IFN-γ, whereas anti-CD4 lost therapeutic potential in the absence of this cytokine. Alternatively, the requirement for IFN-γ for allograft prolongation by anti-LFA-1 therapy was noted only in B6 transplant recipients.
Conclusions.
IFN-γ is not always requisite in islet allograft survival but rather varies according to the molecular target of induction therapy and the genetic background of the transplant recipient.
Lippincott Williams & Wilkins