Expression of common gamma chain signalling cytokines and their receptors distinguishes rejection from tolerance in a rat organ transplant model

abstract Article history:Received 15 June 2012Received in revised form 5 August 2012Accepted 6 August 2012Keywords:Common gamma chain cytokinesLiver transplantationLiver tolerance Background: Signalling through the cytokinecommon γchain ( c) iscrucial for survival ofactivated Tcells.Inits absence, severe combined immunodeficiency ensues and transplanted tissues are not rejected.Methods: To determine whether differences in the availability of γc signalling cytokines correlate withrejection or acceptance, we examined expression of all γc signalling components in organs transplantedbetween PVG donors and DA recipients. In this combination hearts or kidneys are rejected in b10 days whilelivers survive >100 days. Expression of the γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 and theirreceptors γc, IL-2Rα, IL-2Rβ/IL-15Rβ, IL-4Rα, IL-7Rα, IL-9Rα, IL-15Rα and IL-21Rα was determined by real-time PCR pre-transplant and on days 3, 5 and 7 after transplantation.Results: Most increased after transplantation, although there were significantly lower levels of IL-2, IL-2Rα,IL-4and IL-15Rαintolerant livers compared torejecting hearts or kidneys.IL-9wasonly expressed innormalkidneys and decreased during rejection. IL-15 was constitutively expressed and did not change aftertransplantation. IL-21 and IL-21R increased in all transplanted organs to a similar extent. IL-7Rα in liver wasconsiderably increased compared with heart or kidney, consistent with its known inverse relationship toglobal levels of γc signalling.Conclusions: In transplanted livers, acceptance is associated with low levels of all γc cytokines or receptorsexcept IL-21. This is consistent with “dilution” of γc cytokines from a finite clone size of alloreactive T cells inlivers, which are ten times larger than kidneys or hearts.© 2012 Elsevier B.V. All rights reserved.