ABSTRACT
Pioneering studies in mice in the 1950s showed that animals irradiated with otherwise
lethal doses of total body irradiation (TBI) would survive if the spleen was shielded
from irradiation (1,2) or if bone marrow was infused following TBI (3). Subsequent
studies showed that the infused bone marrow cells reestablished lymphohematopoiesis
in the irradiated mice, but the animals generally still died, albeit later than would have
been expected from marrow failure. The syndrome leading to delayed mortality was
termed “secondary disease” (4,5) and clinically resembled strongly what was described
by Billingham and Brent (6) as “runt disease.” These investigators described diarrhea,
weight loss, skin breakdown, sparse fur, odd gait, and retarded growth in unirradiated, neo-
natal mice transplanted with cells from genetically different donors. Both syndromes were
shown to be caused by immunocompetent cells from the donor, hence the current term
graft-vs.-host reaction (GvHR) and the clinical manifestations, graft-vs.-host disease
(GVHD) (7-10). The first observation of GVHD in humans by George Mathe´ in 1960
was made after marrow cells were used to treat survivors of a nuclear accident in Belgrade,
Yugoslavia (11).
