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


CONCLUSIONS
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.
Guo
W H
WH
Division of Pediatric Surgery, Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong SAR, P.R. China.
Tian
L
L
Chan
K L
KL
Dallman
M
M
Tam
P K
PK
D000818:Animals; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D016378:Tissue Transplantation / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents