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ML Cohn, RA Cahill and HJ Deeg
Department of Pediatrics, Georgetown University, Washington, DC.
We investigated in a murine model whether UVB irradiation of
lymphohemopoietic cells would prevent the development of graft-versus- host
disease (GVHD). Preliminary experiments showed that spleen colony (CFU-S)
formation by hemopoietic cells was preserved at UVB doses that eliminated
lymphocyte proliferation. In a parent into F1 model, UVB irradiation (5 to
15 mJ/cm2) of spleen cells added to normal marrow cells prevented the
development of GVHD, whereas all recipients given untreated spleen cells
developed GVHD. Syngeneic recipients of marrow exposed to 2.5 to 10 mJ/cm2
of UVB achieved normal hemopoietic reconstitution. Based on these
observations, B6D2 F1 (H-2b x H-2d) recipients were given 1,000 cGy of
total body irradiation (TBI) followed by transplantation of 5 x 10(6)
parental B6 (H-2b) bone marrow cells and 10 x 10(6) B6 spleen cells, either
unirradiated or exposed to UVB before infusion. All mice transplanted with
cells exposed to 10 or 12.5 mJ/cm2 of UVB survived without GVHD. At 2.5 and
5.0 mJ/cm2, mice showed signs of GVHD, beginning at day 30, and 100% and
80%, respectively, eventually developed chronic GVHD. At 7.5 mJ/cm2, mice
had weight loss, from which 60% recovered and survived without GVHD, while
40% died with GVHD. At 15 mJ/cm2, some recipients died from graft failure,
while some survived without GVHD. All surviving mice were complete
donor-type chimeras. Spleen size and cellularity and in vitro lymphocyte
responses correlated inversely with the development of GVHD. Mice without
GVHD showed specific tolerance to skin grafts from the second parent
strain, while animals with GVHD rejected their skin grafts. Thus, in a
murine model UVB irradiation of transplanted hemopoietic stem cells allows
for hemopoietic reconstitution and prevents GVHD.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
