We studied the effect of transplanting lymphohematopoietic grafts across major histocompatibility barriers into mice conditioned with either single dose 900 rad total body irradiation (TBI), fractionated 17 × 200 rad total lymphoid irradiation (TLI, or single dose 900 rad TLI plus cyclophosphamide (TLI + CY). In all three conditioning regimens, survival following BALB c → C57BL 6 grafting was inversely related to the number of immunocompetent T cells in the donor graft. These findings show that regardless of conditioning protocol (TBI or TLI), it was not possible to protect mice from lethal GvHD when the number of T cells in donor grafts approximated those found in patient bone marrow aspirates. When T cells were eliminated from the donor graft by pretreatment with monoclonal anti-Thy 1.2 plus complement prior to injection into TBI-conditioned recipients, long-term protection from lethal GvHD was indeed possible.
Bibliographical noteFunding Information:
...T his article is dedicated to Robert A. Good on the occasion of his 60th birthday. I This work was supported in part by National Cancer Institute Grants POl-CA-15548, CA-24794 and ROl-CA31618 the Pediatric Oncology Program Project POI-CA21737, University of Minnesota Graduate School Grant 488-0325-4909-02, and the Hubert H. Humphrey Cancer Fund. 2 Abbreviations used: TLI, total lymphoid irradiation; TBI, total body irradiation; BMS, bone marrow plus spleen; CY, cyclophosphamide; GvHD, graft-versus-host disease; C, ComPlement: BM, bone marrow: PBM, peripheral blood mononuclear cell; FITC, fluorescein isothiocyanate conjugated.