Study On The Effects Of Oral Abministration Of Major Histocompatibility Antigems On The Alloimmune Response

Oral tolerance is a state of antigen-specific decreased responsiveness in cell-mediated and/or humoral immunity, induced by feeding antigen. Since oral tolerance is antigen-specific, this approach to immunosuppression. if effective in suppressing graft rejection, would avoid the problems associated with nonspecific immunosuppression. This experiment is to assess the potential value of this approach for modulating allograft rejection. Objective l.To investigate the effects of oral administration of antigens on the alloimmune response;!.To examin the mixed lymphocyte response in vitro and delayed-type hypersensitivity response in vivo after oral administration of antigens;3.To the effectsof oral administration of antigens on the sensitized recipients.4.To discuss the mechanisms of oral tolerance and provid a new thinking for clinical transplant working.Methods Wistar rats were pre-fed allogeneic SD rat splenocytes for 7 days.In an accelerated allograft rejective model,Wistar rats were presensitized with SD skin allografts 7 days before challenging them with SD cardiac allografts.The mixed lymphocyte response in vitro and delayed-type hypersensitivity response in vivo after oral administration of antigens were examined.The cardiac and skin allograft survival of sensitized animals(including feeding group and control group) were observed. 1 .mixed lymphocyte response in vitro: Wistar rats were pre-fed 5 X 107 splenocytes of allgeneic donor SD rats each day.Seven days after the last feeding .PBMCs of recipient rats were tested for their ability to proliferate against donor s PBMCs or third -party stimulators: 2.DTH response: After seven days' s oral administration of donor s antigen,recipient rats were immunized subcutaneously in the inguen with 1X10 donor s or third-party' s splenocytes seven days before challenging them with the same dose of donor s or third-party s splenocyts in the right hind footpad and with 50 u 1 RPMI 1640 in the left hind footpad.Both footpads were measured 24 hr later and the difference in footpad sewelling size was used as a mesrure of DTH: 3.Allografts: 〢fter seven day s feeding of donor s splenocytes, Wistar rats received donor s skin grafts and then the skin allografts survival were observed ; (2)Wistarrats were pre-fed donor splenocytes for seven days,then sensitized with donor s skin,after a sensititation phase of 7 days challenging them with donor s cardiac allografts.The cardiac allograft survival of sensitized animals (including feeding group and control group) were observed. Results l.Fed animals had significantly decreased prolifertion against donor lymphocytes .and only minor reduction in proliferation against lymphocytes of the third-party; 2.There was a significant antigen-specific reduction of DTH response in animals fed allogeneic splenocytes,when compared with unfed control rats; 3. Orally administered alloantigens can prolong the survival of skin or cardiac allografts ; 4. While sensitized control animals reject their cardiac allografts within 2 days, animals prefed with allogeneic splenocytes manintain cardiac allograft survival up to 7 days, similar to that observed in unsensitized control recipients. Conclusions Orally administed alloantigen can down-regulate the immune response to histocompatibility antigens . prolong the survival of skin and heart allografts, prevent sensitization by skin grafts and delay the occurrence of accelerated rejection of vascularized cardiac allografts.