The immune response following small bowel transplantation: I. An unusual pattern of cytokine expression

Acute cell mediated graft rejection is frequently associated with an immune response dominated by cytokines like IL-2 and IFNgamma. While small bowel grafts are rejected acutely, there is little information on the type of immune response generated following transplantation and, in particular, whether the cytokine profile resembles that seen during the rejection of other solid organ grafts. In this paper we compare the expression of cytokines in isolated gut tissue following experimental small bowel transplantation with that in heart grafts. Heterotopic small bowel (n=32) and cardiac (n=32) transplants were performed using the following rat strain combinations: syngeneic Lewis (Lew) > Lew (n=8), blood group D Agouti (DA) > Lew (n=8) and allogeneic Lew > DA (n=8), DA > Lew (n=8). Two rats from each group were sacrificed at 1, 3, 5, or 7 days after transplantation. RNA was prepared separately from gut wall, after removing the Peyer's patches (PPs) and mesenteric lymph nodes (MLNs) and from heart. Cytokine (IL-1alpha, IL-2, IL-4, IL-6, IL-10 and IFNgamma) transcripts were analyzed using semiquantitative RT-PCR. Most notably, transcripts of only a single cytokine, IFNgamma, became progressively elevated with time in the rejecting small bowel grafts. This is in marked contrast to the findings presented here for rat cardiac grafts in which transcripts of all cytokines tested show an increase with rejection. This significant and steady increase in IFNgamma expression occurred before there was any clinical or histological evidence of rejection. These data demonstrate that the mechanisms of rejection in small bowel and other solid organ grafts are likely to be different. Further, the unique rise in IFNgamma expression in the gut wall may be a valuable and early indicator of graft rejection.