Anti-vla4 immunosuppression in two rat small bowel transplant models

Antibodies to cell adhesion molecules prolong allograft survival in some models. This may be partly due to ami-inflammatory effects immediately following revascularization of the altograft. This study investigates whether anti-rat-VLA4 has similar immunosuppressive effects in Lewis rats transplanted either subcutaneously with neonatal bowel (avascular model) or heterotopically (immediately vascularized model)) with adult Brown Norway (BN) small bowel. Transplanted animals were either left untreated or given anti-VLA4 (100 mg/kg/day for five days, IP). Graft rejection was defined by dusky, nacrotic stoma and increased stomal output, at which time the animal was sacrificed - Peripheral blood, spleen, native bowel and allograft intraepithelial and lamina propria lymphocytes were harvested. NK cells have been reported to be active both in rejection and in QVHD, so NK activity against YAC-I cells was assessed. Graft survival was slightly, but significantly prolonged by this short course of antl-VLA4 (untreated: 5.3 days; + anti-VLA4: 8.7 days). No significant differences were seen in NK responses, although anti-VLA4 treatment led to slightly Increased NK activity in syngeneb transplants and allografts from animals treated with antiVLA4 showed somewhat decreased NK activity. We conclude that short-term, low-dose anti-VLA4 does have some effect on graft survival. This effect is not dependent on immediate connection with the host circulation, since the response was similar in both avascular and immediately vascularized allografts. The effects on NK activity appear to be minimal, even though interaction of NK cells with VLA-4 - VCAM has been demonstrated previously.