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Allogeneic Marrow Transplantation after Total Lymphoid Irradiation (TLI): Effect of Dose/Fraction, Thymic Irradiation, Delayed Marrow Infusion, and Presensitization¹

From the Division of Immunology, Department of Medicine, the Howard Hughes Medical Institute Laboratory, Stanford Medical Center, and the Division of Radiotherapy, Stanford University School of Medicine, Stanford, California 94305

Abstract

BALB/c mice infused with 30 x 10⁶ C57BL/Ka bone marrow (BM) cells 1 day after treatment with fractionated total lymphoid irradiation (TLI) (17 fractions of 200 rads each) became stable mixed chimeras without clinical graft-vs-host disease (GVHD). Mice given 18 fractions of 100, 50, or 25 rads each followed 1 day later by C57BL/Ka BM did not become chimeric, indicating that a critical cumulative radiation dose is required for this effect. Animals given TLI with lead shielding placed over the thymus also developed stable chimerism without GVHD. Thus susceptibility to tolerance induction and protection from GVHD after TLI and allogeneic BM transplantation is not due to alteration of the thymic microenvironment by fractionated irradiation. A delay of 7 or 21 days between completion of TLI and BM administration resulted in a high incidence of graft rejection. Sensitization to minor histocompatibility antigens of the BM donor strain by blood transfusion either before or during TLI resulted in marrow graft rejection in a high percentage of animals.

Footnotes

¹ This work was supported by National Institutes of Health Grants AI 11313, CA10372, and by the Howard Hughes Medical Institute.

² Postdoctoral Fellow, Howard Hughes Medical Institute.

³ Investigator, Howard Hughes Medical Institute.

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