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Authors Dutta P, Dart M, Roenneburg DA, Torrealba JR, Burlingham WJ
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Journal Am. J. Transplant. Volume: 11 Issue: 6 Pages: 1296-301
Publish Date 2011 Jun
PubMed ID 21449933
PMC ID 3110527

CD4⁺ Tregs specific for noninherited maternal antigens (NIMA ) are detectable in some but not all B6 × BDF₁ backcross, H-2(b) homozygous offspring, and their presence is strongly correlated with extent of maternal (BDF₁) microchimerism. We hypothesized that the level of pretransplant donor antigen-specific Tregs could predict allograft tolerance. To test this idea, mice were screened for bystander suppression in a DTH assay, followed 1 week later by DBA/2 heterotopic heart transplantation. NIMA -exposed, H-2(b) offspring that failed to suppress DTH uniformly rejected heart allografts (12/12) by d15. In contrast, 5/6 NIMA -exposed DTH ‘regulators’ accepted their allografts >100 days. The defect in ’nonregulator" offspring could be corrected by transfer of CD4⁺CD25⁺, but not CD4⁺ CD25 or CD8⁺ T cells from transplant acceptor mice. In conclusion, donor-specific T reg screening of F1 backcross offspring correctly predicted which recipients would accept a heart allograft. If translated to the clinic, similar pretransplant Treg screening could greatly enhance the effectiveness of tolerance as a clinical strategy in transplantation between family members.

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