Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes: Resemblance to chronic graft-versus-host disease

William E. Beschorner, Allan D. Hess, Charlotte A. Shinn, George W. Santos

Research output: Contribution to journalArticle

Abstract

Syngeneic rat radiation chimeras treated transiently with cyclosporine (CsA) often develop a GVHD-like syndrome after discontinuing the drug. CsA also causes medullary involution and loss of medullary epithelium in the thymus. Chronic graft-versus-host disease (GVHD), a late occurring syndrome following bone marrow transplantation with many features of autoimmune diseases, is thought by many to result from a thymic deficiency leading to a failure to develop specific tolerance for the host. A direct connection between a thymic deficiency and chronic GVHD was tested by transferring thymocytes from CsA-treated syngeneic Lewis chimeras into irradiated Lewis secondary recipients. Nine of 10 of these recipients had evidence of chronic GVHD in skin biopsies taken at 3 weeks posttransplant or in the autopsies at 5 weeks. Changes included characteristic lichen planuslike infiltrates and sclerodermalike changes in the skin, characteristic infiltrates and myositis of the tongue, often chronic hepatitis with bile duct injury, and interstitial and ductal infiltrates in the serous salivary glands. Immunoperoxidase stains of the skin and tongue infiltrates showed a marked predominance of W3/25+:OX8– lymphocytes. The hair follicles had increased expression of la antigen. The thymus in the secondary recipient had variable thymocyte reconstitution of the cortex and a mild to marked reduction in the relative size of the medulla. Stains for cytokeratin showed a moderate to marked reduction of cortical epithelium and marked to total loss of the medullary epithelium. These studies demonstrate that the features of post-CsA syngeneic GVHD resembling chronic GVHD result from an abnormal thymic microenvironment. They also provide additional evidence linking a thymus deficiency with chronic GVHD.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalTransplantation
Volume45
Issue number1
StatePublished - 1988

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Graft vs Host Disease
Thymocytes
Cyclosporine
Thymus Gland
Epithelium
Tongue
Skin
Coloring Agents
Radiation Chimera
Lichens
Myositis
Hair Follicle
Chronic Hepatitis
Keratins
Bile Ducts
Salivary Glands
Bone Marrow Transplantation
Autoimmune Diseases
Autopsy
Lymphocytes

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes : Resemblance to chronic graft-versus-host disease. / Beschorner, William E.; Hess, Allan D.; Shinn, Charlotte A.; Santos, George W.

In: Transplantation, Vol. 45, No. 1, 1988, p. 209-215.

Research output: Contribution to journalArticle

Beschorner, William E. ; Hess, Allan D. ; Shinn, Charlotte A. ; Santos, George W. / Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes : Resemblance to chronic graft-versus-host disease. In: Transplantation. 1988 ; Vol. 45, No. 1. pp. 209-215.
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