Simultaneous liver grafting in the Lewis (RT1(1))-to-DA (RT1a) rat str
ain combination protects small intestinal grafts from rejection. The p
resent study examined host immune responses after combined small bowel
/liver transplantation (SBL) in this model. Orthotopic liver transplan
tation and heterotopic small intestinal transplantation were performed
simultaneously and compared with isolated small bowel allografts (SBA
) and isolated small bowel isografts (SBI). All rats were sacrificed o
n postoperative day (POD) 7 or 14 for immunological and histological s
tudies. The mean time to rejection of the SBA was 6.6 +/- 0.3 days. In
contrast, there was no clinical or histological evidence of intestina
l rejection in SBL recipients during the 14 days of follow-up. The SBL
recipients showed clinical and histological evidence of graft-versus-
host disease (GVHD). Lmphocyte proliferation and IL-2 production in re
sponse to donor antigens were suppressed after SBL transplantation com
pared with the SBA or the SBI controls (P < 0.05). Cell-mediated cytot
oxicity and lymphocytotoxic antibody production against donor cells we
re also significantly inhibited in the SBL recipients compared with th
e SBA control group (P < 0.05). We conclude that SBL transplantation i
n the Lewis-toDA rat strain combination: (1) suppresses host alloimmun
e responses, (2) prevents early intestinal rejection, and (3) favors t
he development of GVHD.