Immune responses of graft mesenteric lymph node in small bowel transplantation.
BACKGROUND
The high proportions of lymphoid tissues are thought to be one of the underlying factors inducing severe allograft rejection following small bowel transplantation. Mesenteric lymph nodes (MLN) contained in the intestinal graft are not only a source of donor-derived professional antigen-presenting cells, but also offer a field for immune interaction between donor and host cells. We investigated immune responses in graft MLNs with or without FK506 to develop a novel strategy to control small bowel allograft rejection.


METHODS
Heterotopic small bowel transplantations were performed from Brown Norway donors to Lewis recipients. Changes in population of lymphocytes, expressions of costimulatory molecules, apoptosis, and cytokine profiles in graft MLNs were evaluated.


RESULTS
The increase in apoptotic cells and cytokine responses relating to rejection in the graft MLNs developed prior to those in graft jejunum. While donor lymphocytes in graft MLNs were rapidly replaced to host-derived lymphocytes independent of FK treatment, increase in CD8(+) T cells in host population was seen only in recipients without FK506 treatment. The expressions of B7 molecules on donor cells in graft MLNs were significantly lower in the recipients with FK treatment.


CONCLUSIONS
Immune responses in graft MLNs have significant impact on the outcome of the small bowel allograft. Apoptosis of graft MLN cells was well correlated with and ahead of progression of acute rejection. Modulation of costimulatory molecules on donor-derived MLN cells in the allograft and specific suppression of host CD8(+) T cells are possible ways to control severe rejection after allogeneic small bowel transplantation.
Kanokogi
Hideki
H
First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
Ko
Saiho
S
Kanehiro
Hiromichi
H
Hisanaga
Michiyoshi
M
Tatekawa
Yukihiro
Y
Kanamura
Tetsuhiro
T
Okayama
Junji
J
Nakajima
Yoshiyuki
Y
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D017209:Apoptosis; D018122:B7-1 Antigen / Q000187:drug effects; D051940:B7-2 Antigen; D016207:Cytokines / Q000235:genetics; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation*; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D008643:Mesentery; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014019:Tissue Donors
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D012333:RNA, Messenger