Prevention of Type 1 Diabetes with Major Histocompatibility Complex–Compatible and Nonmarrow Ablative Hematopoietic Stem Cell
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Donor B-cells predominate in islet infiltrates of chimeric mice but are not required for diabetes protection. A: Immunohistochemistry of an islet from a B6.H-2g7 bone marrow into NOD chimera 6 months after transplantation. Shown are stains of serial sections of the same islet. The findings
are representative of immunohistochemical analyses performed on islets from diabetes-free chimeric mice. Most islets in the
chimeras were minimally infiltrated (Table 2); however, the few islets that showed severe infiltrates were strongly positive for B220+ and CD45.2+ (donor derived). Infiltration with CD4+ and CD8+ T-cells and Mac-1+ cells were minimal. B: Diabetes-free survival of NOD mice engrafted with B-cell–deficient B6.H-2g7 bone marrow. Lethally irradiated (950 cGy) NOD mice that were transplanted with bone marrow from B-cell–deficient B6.H-2g7.μMT−/− donors (○) were 100% protected from diabetes as were control NOD mice reconstituted with B6.H2g7 bone marrow (•). Control NOD mice reconstituted with syngeneic NOD bone marrow (▾) developed diabetes (P < 0.036). C: Lethally irradiated NOD mice transplanted with HSCs from T- and B-cell–deficient B6.H-2g7.SCID mice (•) demonstrated significant protection from diabetes compared with syngeneic recipients (▾) (P < 0.002).