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Although there is evidence linking hematopoietic chimerism induction and solid organ transplant tolerance, the mechanistic requirements for chimerism-induced tolerance are not clearly elucidated. To address this, we used an MHC-defined primate model to determine the impact of impermanent, T cell-poor, mixed-chimerism on renal allograft survival. We compared two cohorts: one receiving a bone marrow and renal transplant ("BMT/renal") and one receiving only a renal transplant. Both cohorts received maintenance immunosuppression with CD28/CD40-directed costimulation blockade and sirolimus. As previously demonstrated, this transplant strategy consistently induced compartmentalized donor chimerism, (significant whole-blood chimerism, lacking T cell chimerism). This chimerism was not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival time (MST, 76 days) was not significantly different than the renal transplant alone MST (85 days, p = 0.46), with histopathology documenting T cell mediated rejection. Flow cytometric analysis revealed significant enrichment for CD28-/CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between CD28-negative Tem and costimulation blockade-resistant rejection. These results suggest that in some settings, transient T cell-poor chimerism is not sufficient to induce tolerance to a concurrently placed renal allograft and that the presence of this chimerism per se is not an independent biomarker to identify tolerance.
Pubmed ID: 22642491
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Center that facilitates the optimal use of nonhuman primate models in biomedical research by identifying, developing, characterizing and producing reagents for monitoring or modulating immune responses. They distribute non-human primate-specific antibodies for in vitro diagnostics, as well as develop and produce primate recombinant antibodies for in vivo cell depletion or modulating immune responses.
View all literature mentionsCenter that facilitates the optimal use of nonhuman primate models in biomedical research by identifying, developing, characterizing and producing reagents for monitoring or modulating immune responses. They distribute non-human primate-specific antibodies for in vitro diagnostics, as well as develop and produce primate recombinant antibodies for in vivo cell depletion or modulating immune responses.
View all literature mentions