A correlation between conditioning and engraftment in recipients of MHC-mismatched T cell-depleted murine bone marrow transplants

C. C.B. Soderling, C. W. Song, B. R. Blazar, D. A. Vallera

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

We studied engraftment in a murine model of allogeneic bone marrow (BM) transplantation. Recipient C57BL/6 (H-2(b)) mice were conditioned with single-dose (9 or 7.5 Gy) total body irradiation (TBI), fractionated (4 x 3.3 Gy) TBI, hyperfractionated (8 x 1.65 Gy) TBI, 2 x 120 mg/kg cyclophosphamide (CY) followed by 7.5 Gy TBI, or 300 mg/kg CY followed by 9 Gy total lymphoid irradiation (TLI). Conditioned mice were transplanted with BALB/c (H-2(d)) BM supplemented with splenocytes (BMS) to facilitate graft-vs-host disease (GVHD). Ex vivo T cell depletion of the BMS with anti-Thy-1.2 antibody and complement protected recipients from lethal GVHD. Engraftment was measured in transplanted animals by serotyping peripheral blood mononuclear cells with anti-H-2-specific antibodies and complement. Mice that were given a T cell-depleted BMS transplant after conditioning with 9 Gy TBI, fractionated TBI, or CY plus TBI showed a 99 to 100% incidence of engraftment. However, if the T cell-depleted graft was given to mice conditioned with hyperfractionated TBI, 7.5 Gy TBI, or CY plus TLI, only 3 to 32% of the animals engrafted. BM which was not T cell-depleted engrafted in 63 to 100% of the mice regardless of the conditioning used. Nonengrafted mice tested with anti-host type antibody demonstrated autologous recovery. We conclude that engraftment or failure/rejection of BM in transplanted mice is determined in part by a dynamic equilibrium between T cells present in the donor graft and the surviving hemopoietic cells in the conditioned recipient. More intensive conditioning of the recipient allows engraftment of T cell-depleted, mismatched BMS. Such conditioning is not limited to a single modality, but can be achieved with single-dose TBI, fractionated TBI, or with TBI combined with CY. These findings have timely and important implications for the current understanding of engraftment in human allogeneic BM transplantation following T cell depletion.

Original languageEnglish (US)
Pages (from-to)941-946
Number of pages6
JournalJournal of Immunology
Volume135
Issue number2
StatePublished - Dec 1 1985

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