Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 1, Pages 165-173Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.1.165
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Funding
- NHLBI NIH HHS [P01 HL018646-300014, P01 HL018646-280014, R01 HL049915-15, R01 HL049915, P01 HL018646, P01 HL018646-290014, R01 HL049915-14, R01 HL049915-13A1] Funding Source: Medline
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Allogeneic bone marrow chimerism induces robust systemic tolerance to donor alloantigens. Achievement of chimerism requires avoidance of marrow rejection by pre-existing CD4 and CD8 T cells, either of which can reject fully MHC-mismatched marrow. Both barriers are overcome with a minimal regimen involving anti-CD154 and low dose (3 Gy) total body irradiation, allowing achievement of mixed chimerism and tolerance in mice. CD4 cells are required to prevent marrow rejection by CD8 cells via a novel pathway, wherein recipient CD4 cells interacting with recipient class II MHC tolerize directly alloreactive CD8 cells. We demonstrate a critical role for recipient MHC class II, B cells, and dendritic cells in a pathway culminating in deletional tolerance of peripheral alloreactive CD8 cells.
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