Role of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft

Abstract

Background/Purpose: Results of small bowel transplantation remain unsatisfactory because of severe immune rejection. The current study aims to elucidate the role of activation of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft and, hence, provide the immunologic basis for developing new therapeutic strategies. Methods: We used an MHC fully mismatched (DA to Lewis) heterotopic rat small bowel transplant model and a unique FK506-based immunosuppressive regimen, which suppresses early acute rejection but does not prevent late acute rejection. Flow cytometric analysis was used to quantitate the number of activated CD4+ and CD8+ T cells in graft and host mesenteric lymph nodes. Results: The survival (mean ± SD) of intestinal allograft was significantly prolonged, from 6.6 ± 0.84 days for the untreated group to 40.7 ± 14.1 days for the FK506-treated group. Activation of CD4+ cells was suppressed significantly in the FK506-treated group on postoperative day 7 compared with the untreated group (29.4% ± 3.55% v 52.83% ± 11.9%; P <.01). Activation of CD8+ cells was similarly suppressed (31.5 ± 10.34% v 48.53 ± 14.34%; P <.05). Interestingly, at late acute rejection, activated CD4+ and CD8+ T cells remained at almost the same low levels as those on postoperative day 7 in the FK506-treated group. The spleen to body weight ratio was significantly increased in the untreated group (0.53 ± 0.07), and slightly increased in the FK treated group (0.27 ± 0.07, on postoperative day 7; 0.24 ± 0.07 at late acute rejection) compared with the syngeneic group (0.18 ± 0.02). Conclusion: The activation of CD4+ and CD8+ T cells was suppressed effectively by early potent immunosuppressive treatment resulting in prolonged survival of intestinal allograft. At late acute rejection, the CD4+ and CD8+ T cells remained at low-level activation status, in contrast to the surge of CD4+ and CD8+ activation during early acute rejection. This suggests that persistent T cell activation even at low level is sufficient to cause the late acute rejection eventually. A therapeutic strategy targeting these cells is needed for long-term engraftment. J Pediatr Surg 36:352-356. Copyright © 2001 by W.B. Saunders Company.