Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

Journal Article · Thu Jan 15 04:00:00 EST 1987 · J. Immunol.; (United States)

OSTI ID:7083043

Schwartz, E; Lapidot, T; Gozes, D; Singer, T S; Reisner, Y

Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C/sub 3/H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of /sup 125/IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected.

• Research Organization: Weizmann Institute of Science, Rehovot, Israel
• OSTI ID: 7083043
• Journal Information: J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 2; ISSN JOIMA
• 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.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CELL CULTURES
CLONE CELLS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
EXTERNAL IRRADIATION
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNOSUPPRESSION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IRRADIATION
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
SPLEEN CELLS
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION