http://radiology.rsnajnls.org/cgi/content/full/2461062075/DC1.

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Spontaneous orthotopic liver allograft acceptance associated with microchimerism in mice induces tolerance to subsequent skin or heart transplants from the donor but not third-party animals. Despite in vivo hyporesponsiveneu, in vitro MLC and CTL assays showed continuing anti donor reactivity. Cells isolated from recipients' spleens and grafted livers, when tested in MLC and CTL assays, were antidonor reactive out to 3 months to the same degree as splenocytes obtained from either naive or presensitized (with skin or heart) mice. Nevertheless, passive transfer of splenocytes or liver lymphocytes from liver tolerant mice, but not naive or sensitized donor strain mice, were able to prolong skin graft survival significantly in naive irradiated recipients. By using a strain combination in which the donor but not the recipient expressed the stimulatory endogenous super-Ag (MIs,), it was possible to determine whether super-Ag-reactive T cells bearing VIJ5 and VlJl1 were deleted or anergic. Phenotypic analysis of cells isolated from recipients' spleens and grafted livers (up to 90 days after transplant). when compared with naive animals. showed no significant difference in VIJ5 and VfJll TCR expression. Additionally, when these isolated spleen cells were tested for antibody-mediated stimulation. both anti-VlJ6 and VfJll TCR mAb led to marked proliferation of cells obtained from naive and liver-transplanted recipients. but as expected, proliferation was very low in cells from naive donors. These results suggest that liver transplantation induces donorspecific tolerance in vivo, which may not be reflected in in vitro proliferative and cytotoxicity assays (split tolerance). Furthermore. this tolerance does not seem to be induced by clonal deletion or anergy of minorlymphocyte-stimwating-antigen-reactive T cells in the recipients.

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