Enhanced in situ expression of NF-kappaBp65 is an early marker of intestinal graft rejection in rats.
BACKGROUND
Although intestinal transplantation provides a unique situation of free access to the graft because of the presence of temporary enterostomas, evaluation of local immunosuppression is still an unresolved issue and may constitute one of the causes of grafting failure.


OBJECTIVE
To study in a rat model of allogeneic intestinal transplantation the expression of transcription factors involved in lymphocyte activation in situ in the graft and to identify factors reflecting the efficiency of drug immunosuppression.


METHODS
Intestinal transplantation was performed in a Brown Norway (RT1n-donors)-Lewis (RT1(l)-recipients) rat strain combination. The animals were treated with tacrolimus to induce tolerance or left untreated. Syngeneic intestinal grafts and intestine from donor rats with peritonitis were used as controls. NF-kappaBp65, p-c-Jun, interleukin 2 receptor (CD25), and major histocompatibility complex class II antigen (OX-6) expression was studied in graft biopsies on days 2 and 5 by immunohistochemistry.


RESULTS
On day 2, before the onset of histologic signs of rejection, the number of cells expressing NF-kappaBp65 in the pericryptic lamina propria was significantly higher in untreated recipients of allogeneic grafts than in the other groups (P = .009). NF-kappaBp65 expression then fell between days 2 and 5 (P = .009). Classic markers of T-cell activation (CD25 and OX-6) were expressed during rejection in the lamina propria and on crypt enterocytes, respectively. p-c-Jun expression did not differ among the 3 groups.


CONCLUSIONS
NF-kappaBp65 expression in intestinal grafts is a precocious sign of local activation during rejection and could thus serve to optimize the management of immunosuppressive therapy.
Cheikhelard
Alaa
A
INSERM E-0212, Faculté Necker Enfants-Malades, 75730 Paris Cedex 15, France.
Go
Seitetsu
S
Canioni
Danielle
D
Leborgne
Michèle
M
Brousse
Nicole
N
Révillon
Yann
Y
Cerf-Bensussan
Nadine
N
Sarnacki
Sabine
S
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D006084:Graft Rejection; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007422:Intestines / Q000637:transplantation*; D008213:Lymphocyte Activation; D051381:Rats; D051996:Transcription Factor RelA / Q000032:analysis / Q000096:biosynthesis*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D051996:Transcription Factor RelA