title: Pretransplant immune-regulation predicts allograft tolerance.
abstract: CD4⁺ Tregs specific for noninherited maternal antigens (NIMA(d) ) 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(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.
authors: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors: P
authors: P
authors: Dutta
authors: M
authors: M
authors: Dart
authors: D A
authors: DA
authors: Roenneburg
authors: J R
authors: JR
authors: Torrealba
authors: W J
authors: WJ
authors: Burlingham
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit