Allogeneic Antigens Door Intravenous Inoculation Induce Specific Immune Suppression And To Extend The Experimental Study Of Different Strains Of Mice Heart Graft Survival

The interposition of the liver between the gastrointestinal tract and the general circulation provides metabolic advantages. In addition, this interposition is also immunologically important, because the liver and portal system appear to function to prevent sensitization to antigens introduced to the liver via the portal venous (p.v.) route. In fact, presentation of many antigens via gastrointestinal tract or by injection into p.v. circultion not only avoids immunization but also tends to favor tolerance induction, in contrast to the presentation via other routes. Thus, specific immunologic tolerance induced by intragastric or p.v. route has been described as epatic tolerance or ortal venous tolerance. Objective This study is aimed to define the change of the level of immunoreactions to allogeneic cells after receiving portal venous inoculation with allogeneic cells in mice and the involved mechanisms of allospecific tolerance induced by portal venous administration of donor antigen.To investigate the effect of portal venous inoculation of donor-specific splenocytes combined with cyclosporin A(CsA) administration on cardiac allograft survival in mice. Method lO7splenocytes from NIH/q or third-party C57/BL spleens were injected into BALB/C hosts via the host portal vein or the systemic vein. BALB/C mice also received 10~ neuraminidase- treated spelenocytes from NIH/q via the systemic vein (n=8). Gadolinium chloride (GaOL3), a rare earth metal known to inhibit Kupffer cell phagocytosis, was given (7mg/kg) I day before spelenocytes of NIH/q injection via BALB/C portal vein (n=8). 7 days 4 later, BALB/C mice were inoculated on the dorsal flanks with 1O7NIH/q splenocytes depleted of erythrocytes. Mixed lymphocyte reation (MLR) of BALB/C to NIH/q mice alloantigens was investigated and anti-NIH/q delayed-type hypersinsitivity (DTH) responses was assessed by directly challenging i07 NIH/q splenocytes in a volume of 25 1.1 I into BALB/C hind footpads 7 days later. Heterotopic cardiac transplantation between the fully allogenic NIH/q and BALB/C strain mice were performed. A modified procedure of neonatal heart-in-ear transplantation, as originally described by Fulmer et al, was used. We prepared donor splenocytes from NIH/q or third-party C57BL spleens for BALB/C hosts and injected the splenocytes preoperatively via the host portal vein or the systemic vein. The neonatal heart-in ear transplantation was performed a week later. The hosts were treated with a short course of the immunosuppressive agent, C5A(4mglkg,-7? days perioperatively). Result Portal venous inoculation of NIH/q splenocytes significantly abolished the capability of the animals to develop MLR responses and DTH responses to NIH/q alloantigens as induced by subcutaneous immunization with NIH/q splenocytes (P<0.05, n=8), in which the stimulation index (SI) of MLR was 3.51? 55 and the footpad increment of DTH was 7.4 ?0.6 (102mm). NIH/q mice splenocytes injected via the systemic vein or third-party C57/BL mice splenocytes injedted via the portal vein did not abolish the capability of the animals to develop MLR responses and 0TH responses to NIH/q alloantigens (P>0.05, n=8), in which the SI of MLR was 34.83 ? 90 and 35~33?2 54 the footpad increment of DTH was 23.5? 1.7(102mm) and 23.9?.8(102mm). Either intrave...