Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade

Autor: Sinda Bigenzahn, Ines Pree, Christoph Klaus, Nina Pilat, Benedikt Mahr, Elisabeth Schwaiger, Patrick Nierlich, Friedrich Wrba, Thomas Wekerle
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Journal of Immunology Research, Vol 2016 (2016)
Druh dokumentu: article
ISSN: 2314-8861
2314-7156
DOI: 10.1155/2016/8635721
Popis: Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2×107 bone marrow cells (BMC) from either of three donor strains: Balb/c (H2d) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10.D2 (H2d) or B10.A (H2a) (both MHC mismatched, but mHAg matched). Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p
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