Mixed Chimerism with MHC-Matched Bone Marrow Transplantation Results in Dominant Protection From Autoimmune Diabetes (83.8)
| Autor: | Ronald Gill, Marilyne Coulombe, Carrie Toews, Liping Yu, George Eisenbarth |
|---|---|
| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:83.8-83.8 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Allogeneic mixed chimerim can prevent disease onset in Type 1 diabetes. While bone marrow (BM) allografts from MHC-mismatched donors can prevent disease in NOD mice, levels of mixed chimerism can be variable and unstable. Also, MHC-mismatched BM usually involve donor T cell depletion, increasing risk for graft-versus-host reactivity. Therefore, we tested the ability of MHC-matched donors to protect NOD mice from disease. Young female NOD mice were irradiated (2 x 450R) and grafted with the following BM donors: (1) Disease-prone NOD (H-2g7), (2) MHC-matched, disease-resistant C57Bl/6.H-2g7 (B6.H-2g7), (3) MHC-mismatched, disease-resistant C57Bl/6 (B6), or (4) Mixtures of disease-prone + disease-resistant BM. Importantly, donor BM was depleted of mature T and B cells. Recipients of only NOD BM recapitulated diabetes in 31/33 (94%) recipients by 30 weeks. Conversely, recipients of B6.H-2g7 BM alone did not develop diabetes (0/26). Mixed NOD + B6.H-2g7 BM grafts resulted in marked disease protection in 27/30 recipients (p 40-50% NOD) for ≥ 30 weeks. Thus, MHC-matched BM allografts permits dominant disease protection and stable macro-chimerism in NOD mice. Also, disease-prone MHC is not an intrinsic barrier to autoimmune regulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|