Abstract
The objective of this study was to determine the effectiveness of total lymphoid irradiation (TLI) treatment of the induction of unresponsiveness to allogeneic whoie fetal pancreas tissues, which are highly immunogenic (control survival times in three combinations: <10 days). Streptozotocin-diabetic Lewis male rats were irradiated 4–5 times a week with a daily dose of 200 rads under a lead shield covering the skull, lungs, hind legs, pelvis, and tail. The spleen, thymus, and major lymph nodes were exposed to radiation. When the desired total TLI dose was reached, the rats were injected with 1–3 × 108 donor-type aduit bone marrow cells within one day after TLL, followed by fetal pancreas transplants under the kidney capsule between 1 and 35 days after TLI. Three strain combinations with immunogenetic barriers ranging from moderate (non-Rt1) to strong (Rt1) were used to determine a minimum effective dose for the permanent acceptance of pancreas allografts. Fischer → Lewis fetal pancreases identical at Rt1 but differing at multiple non-Rt1 loci were accepted permanently in the recipients who were treated with 1200 rads TLI and 108 donor bone marrow cells. Diabetes was permanently reversed or significantly improved. A minimum effective TLI dose in this combination was found to be 1000 rads. (Buffalo × Lewis)F1 → Lewis fetal pancreas grafts across strong Rt1 barriers required at least a total TLI dose of 2600 rads, when semiallogeneic F1 bone marrow cells were used. A higher dose (3000 rads) was required, when 1–3 × 108 of fully allogeneic Buffalo bone marrow ceils were grafted. Even then, only a part of the group of treated Lewis became unresponsive to donor tissues. Removal of the pelvic shield, however, resulted in consistent development of a high percentage of donor bone marrow chimera and permanent acceptance of allografts in Buffalo or F1 × Lewis combinations. This procedure exposed the whole pelvic area and part of the femur along with the portions exposed by the complete lead shield procedure. Donor-type bone marrow grafting, in addition to TLI, was essentiai for permanent acceptance of allografts.
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