Graft versus Host Disease in Rats Made Tolerant for Organ Allografts (original) (raw)
1997, Journal of Surgical Research
cific immunosuppression. The potential solution to Tolerance for organ allografts would eliminate acute these problems would be the induction of donor specific and chronic rejection as well as the need for nonspetolerance. Additionally, this would allow for the succific immunosuppression. A potential hazard of tolercessful grafting of highly immunogenic organs such as ance is the susceptibility to graft vs host disease the small bowel where clinical success has been limited (GVHD) due to unresponsiveness to alloantigen. This because of infectious complications. Tolerance inducstudy sought to determine if our model of tolerance tion could be complicated by an unopposed reaction induction results in susceptibility to GVHD. Chimeras of the graft against the host when immune elements were created by transplantation of T-cell depleted ACI contained within the graft are of sufficient quantity. and Lewis bone marrow into lethally irradiated Lewis This phenomenon of graft vs host disease (GVHD) has rats. Chimerism was determined post-BMTx by flow been widely studied in experimental studies of bone cytometric analysis of recipient spleens for the presmarrow transplantation [1, 2] and has been reported ence of ACI cells. ACI/Lew chimeras (ALC), animals sporadically following liver, lung, and small bowel that reconstituted only with syngeneic (Lewis) martransplantation. In order for GVHD to occur, three crirow (so-called failed chimeras), and ACI/Lew F1 teria must be met: (a) immunologic mismatch between (LACF 1 ) hybrid rats were all given 200 1 10 6 ACI splengraft and host, (b) lack of host response against graft ocytes i.v. Animals were examined for evidence of for a period of time long enough for the graft to mount GVHD. GVHD was quantified using the popliteal a response against the host, and (c) sufficient lymphoid lymph node enlargement assay. All LACF 1 (n Å 6) rats tissue in graft to mount a significant response against developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n Å 6) developed fatal the host . In experimental small bowel transplanta-GVHD. Animals that reconstituted only with syngeneic tion, the phenomenon of GVHD in the parent to F1 Lewis marrow (failed chimeras) showed no signs of direction (Lew r Lewis/Brown-Norway F1) has been illness. GVHD was confirmed histologically and immudescribed . The susceptibility of the host to GVHD nohistochemically. Failed chimeras receiving ACI under conditions of experimentally induced tolerance splenocyte challenge showed no evidence of GVHD hishas not been investigated, but is a concern for the futologically. Popliteal lymph node enlargement indices ture application of strategies to induce tolerance, parreflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results TABLE 1 in susceptibility to GVHD if enough donor lymphoid Summary of Results Following Splenocyte Injection tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed GVHD GVHD Mean
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