THE IMMUNE-RESPONSE FOLLOWING SMALL-BOWEL TRANSPLANTATION .2. A VERY EARLY CYTOKINE RESPONSE IN THE GUT-ASSOCIATED LYMPHOID-TISSUE

The small bowel has a unique amount of closely associated lymphoid tis sue in the form of mesenteric lymph nodes (MLNs) and Peyer's patches ( PPs). It is rather unclear how this may affect the immune response to transplants involving small bowel. It is clear, however, that host-der ived leukocytes infiltrate this lymphoid tissue very rapidly after tra nsplantation of small bowel, which suggests the possibility of an earl y immune response within this compartment. To in vestigate this possib ility, we analyzed, using a semiquantitative reverse transcriptase-pol ymerase chain reaction, the level of cytokine transcripts within isola ted MLNs and PPs for the first 7 days after small bowel transplantatio n.Heterotopic small bowel (n=32) transplants were performed using the following rat strain combinations: syngeneic Lewis (Lew)-->Lew (n=8), blood group D Agouti (DA)-->DA (n=8), allogeneic Lew-->DA (n=8), and a llogeneic DA-->Lew (n=8). Two rats from each group were killed at 1, 3 , 5, and 7 days after transplantation. RNA was prepared separately fro m PPs and MLNs before analysis of transcripts for interleukin (IL) 2, IL-4, IL-10, IL-6, IL-1 alpha, and interferon (IFN) gamma. No increase in transcripts for IL-2 or IL-10 was observed in either PPs or MLNs o f syngeneic grafts. A small rise in IL-6, IL-1 alpha; and IFN-gamma tr anscripts was seen in MLNs and IFN-gamma transcripts in PPs of syngene ic grafts. In contrast, in allografts an extremely early increase in c ytokine transcripts was observed; all cytokine transcripts tested were elevated within the first 24 hr after transplantation. Indeed, the pe ak response of both IL-2 and IL-10 occurred within 1 to 3 days after g rafting. This early immune response in the lymphoid tissue may not be controlled by immunosuppression delivered only at the time of transpla ntation and therefore may be responsible for the difficulty in achievi ng adequate immunosuppression in small bowel transplantation.