Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

Journal Article · Mon May 15 04:00:00 EDT 1989 · Blood; (USA)

OSTI ID:5599929

Lapidot, T; Terenzi, A; Singer, T S; Salomon, O; Reisner, Y ^[1]

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1. Weizmann Institute of Science, Rehovot (Israel)

A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum.

• OSTI ID: 5599929
• Journal Information: Blood; (USA), Journal Name: Blood; (USA) Vol. 73:7; ISSN BLOOA; ISSN 0006-4971
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BLOOD FORMATION
BODY
BODY FLUIDS
BONE MARROW CELLS
CHIMERAS
CONNECTIVE TISSUE CELLS
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNITY
IRRADIATION
LECTINS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MOSAICISM
MYLERAN
ORGANS
RADIATION CHIMERAS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
RODENTS
SOMATIC CELLS
SPLEEN
STEM CELLS
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION