Pretransplant Immune‐Regulation Predicts Allograft Tolerance

CD4 + Tregs specific for noninherited maternal antigens (NIMA d ) are detectable in some but not all B6 × BDF 1 backcross, H‐2 b homozygous offspring, and their presence is strongly correlated with extent of maternal (BDF 1 ) 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 d ‐exposed, H‐2 b offspring that failed to suppress DTH uniformly rejected heart allografts (12/12) by d15. In contrast, 5/6 NIMA d ‐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 neg 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.