The Journal of Immunology, Vol 138, Issue 2 460-465, Copyright © 1987 by American Association of Immunologists

ARTICLES

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

E Schwartz, T Lapidot, D Gozes, TS Singer and Y Reisner

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. C3H/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 125IUdR. 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. These results suggest that resistance to T cell-depleted allogeneic bone marrow in irradiated mice closely correlates with the frequencies of residual host clonable T cells detectable by conventional immunologic assays.

This article has been cited by other articles:

				P. A. Taylor, M. J. Ehrhardt, M. M. Roforth, J. M. Swedin, A. Panoskaltsis-Mortari, J. S. Serody, and B. R. Blazar Preformed antibody, not primed T cells, is the initial and major barrier to bone marrow engraftment in allosensitized recipients Blood, February 1, 2007; 109(3): 1307 - 1315. [Abstract] [Full Text] [PDF]

				W. R. Drobyski, H. C. Morse III, W. H. Burns, J. T. Casper, and G. Sandford Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene Blood, April 15, 2001; 97(8): 2506 - 2513. [Abstract] [Full Text] [PDF]

				I Lubin, Y Faktorowich, T Lapidot, Y Gan, Z Eshhar, E Gazit, M Levite, and Y Reisner Engraftment and development of human T and B cells in mice after bone marrow transplantation Science, April 19, 1991; 252(5004): 427 - 431. [Abstract] [PDF]