Abstract
Background and aims: In our previous studies, immune response of mixed chimeras to donor skin could be presaged as “reliable tolerance”, “possible tolerance” and “hyporesponsiveness” based upon peripheral chimerism of >3%, 0.2-3% and < 0.2% at graft placement. This study would examine whether postnatal donor lymphocyte infusion could augment chimerism.
Methods: After in utero marrow transplantation, mouse recipients were collected and grouped based upon first month peripheral chimerism of >3%, 0.2-3%, 0.01-0.19%, and undetectable. Postnatal donor lymphocytes (5-10x107) were intravenously infused within 3 days after chimerism examination. Peripheral chimerism was then followed up periodically.
Results: Peripheral chimerism was rapidly boosted up within 2 hours, but eventually returned to pre-booster levels by days 7-14. It suggests an immediate additive effect of injected donor lymphocytes on the transient uprise of chimerism levels. For recipients with peripheral chimerism < 0.2%, postnatal lymphocyte infusion never enhanced peripheral chimerism at the subsequent examination. Chimerism augmentation only succeeded in 4 recipients with 1.22, 1.54, 4.01 and 4.81% chimerism. Their circulating donor cells remained around a level of 2.41-4.85% on day 7 and didn't increase to a level of >10% with multilineage expression until 1-2 months after lymphocyte infusion. However, three of them proved to have GVHD by histological examinations. In addition, lots of recipients, especially with chimerism of >0.2% died unexpectedly 1-12 weeks after infusion.
Conclusions: For low-level chimerism of >0.2%, postnatal donor lymphocyte infusion could augment donor cell levels with a latent period of 1-2 months after infusion, but ofen at the cost of GVHD.
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Chen, JC., Kuo, ML. Postnatal Donor Lymphocyte Infusion Augmented Chimerism at the Cost of GVHD in Low-Level Mixed Chimeras. Pediatr Res 70 (Suppl 5), 429 (2011). https://doi.org/10.1038/pr.2011.654
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DOI: https://doi.org/10.1038/pr.2011.654