Background: Heart transplantation is a lifesaving measure for many infants with severe congenital heart diseases. The acceptance of cardiac allografts without immunosuppression, or operational tolerance, has remained a major goal of transplant immunology research. Tolerance can be achieved by introducing genetically different cells into immature recipients and creating mixed chimerism. Previously, we injected C3H/He (C3H; H-2k) neonates with either fully allogeneic BALB (BALB; H-2d) fetal liver cells (FLC), or semi-allogeneic spleen cells (F1-SP) (BALB×C3H; H-2d/2k). Long-term chimerism was established in neonates injected with F1-SP but not FLC. We hypothesize that cell type of the tolerizing inoculum is more important than allelic differences in establishment of chimerism. Methods: This study compared molecular chimerism established by injection of different cellular inocula. Within 24hr of birth, female C3H neonates were treated with male cellular inocula of fully allogeneic BALB FLC, or F1-FLC, F1-bone marrow (BM) or F1-SP. On the respective days after treatment, tissues were excised (liver, bone marrow, brain, kidney, intestine, heart, thymus, uterus, ovary, spleen, lymph node, tail, bladder, lung and blood) and chimerism was assessed by PCR for the male-specific SRY gene. Results: At 3 and 14 days, chimerism was detected in all treated mice, but was transient in both BALB FLC and F1-FLC treated mice, disappearing by 7 weeks after injection. Only F1-BM and F1-SP treated mice maintained detectable long-term chimerism. Conclusions: Cell type is important in the establishment of long-term chimerism. Our findings will help advance our understanding of the mechanisms of neonatal tolerance induction.

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