Prevention of Type 1 Diabetes with Major Histocompatibility Complex–Compatible and Nonmarrow Ablative Hematopoietic Stem Cell Transplants

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FIG. 1.
FIG. 1.

Diabetes-free survival and donor chimerism of NOD mice engrafted with hematopoietic cells. Eight-week-old pre-diabetic NOD mice were prepared for transplantation with 950 cGy of lethal irradiation followed by infusion of purified HSCs or unmanipulated bone marrow (WBM). A: All recipients engrafted with HSC (▵) or bone marrow (vertical ticks) derived from MHC-matched B6.H-2g7 donors were protected from diabetes development. In contrast, nearly all mice that received NOD HSCs (○) or bone marrow (▪) progressed to hyperglycemia (P < 0.001), although the time to overt disease was delayed compared with untreated NOD mice (▿) (P < 0.001). B: Significant differences in the development of T-cell chimerism were noted after B6.H-2g7 HSC (▴) versus bone marrow (•) transplantation (each symbol represents one mouse). NOD mice reconstituted with purified HSCs showed lower levels of donor-derived T-cells and retained more host T-cells. In contrast, NOD mice reconstituted with bone marrow demonstrated high levels of donor-derived T-cells within 2 months posttransplant (P < 0.001). Over time, donor-derived T-cells slowly increased in HSC-transplanted NOD mice. C: Non–T-cell lineages (B-cells shown here) were predominantly donor derived both in HSC (▵)- and bone marrow (○)-transplanted NOD mice early after transplantation.

This Article

  1. Diabetes vol. 54 no. 6 1770-1779