Journal of Experimental Medicine, Vol 172, 85-94, Copyright © 1990 by Rockefeller University Press
Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes
AC Fischer and AD Hess
Bone Marrow Transplantation Program, Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
The present studies have evaluated the effect of age on the induction of
syngeneic graft-versus-host disease (SGVHD) after syngeneic bone marrow
transplantation (BMT) and cyclosporine (CsA) therapy. The results clearly
document an inverse correlation of age with the incidence of SGVHD.
Virtually a 100% incidence of SGVHD occurs in Lewis rats when syngeneic BMT
and CsA therapy are started when the animals are 4 wk of age. Thereafter,
there is a dramatic decline in the incidence of SGVHD with the increasing
age of the animals. Although the age of the recipient was important, the
most significant effect was the age of the marrow donor. Marrow from
animals 6 mo of age was virtually incapable of eliciting SGVHD after BMT
and CsA therapy. Furthermore, mixing the marrow from mature and immature
animals resulted in a decreased incidence of SGVHD, implicating a
regulatory effect present in the marrow from older rats. This regulatory
effect was due to the presence of mature T cells in the marrow from animals
6 mo of age. Despite the fact that marrow from young animals possesses
mature T lymphocytes, this regulatory activity was absent, suggesting that
the host resistance mediated by T lymphocytes develops as the animal ages.
These data further implicate the importance of a host resistance mechanism
in preventing the induction of SGVHD with CsA, which appears to be mediated
by the clonal inactivation of autoreactive cells.
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