Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: Regulatory role of marrow-derived T lymphocytes

Anne C. Fischer, Allan D. Hess

Research output: Contribution to journalArticlepeer-review

Abstract

The present studies have evaluated the effect of age on the induction of syngeneic graft-versushost 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.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalJournal of Experimental Medicine
Volume172
Issue number1
DOIs
StatePublished - Jul 1 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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