Viral Infection & Salivary Gland Graft-vs. Host Disease

Sheridan, John

Abstract

Graft-versus-host disease (GVHD), a significant complication of bone marrow transplantation (BMT) frequently affects the salivary and lacrimal glands producing a Sjogren's-like syndrome. The primary and secondary clinical effects of GVHD in these glands are similar to those seen with Sjogren's syndrome: dry, burning mouth and incrased incidence of dental caries and candidal infections. Hisopathological findings of GVHD in these tissues appear similar to Sjogren's syndrome with a lymphocytic infiltrate beginning periductally and the later development of epimyoepthelial islands. Other similarities which exist between GVHD of the salivary and lacrimal glands and Sjogren's syndrome include various immunologic abnormalities, associated with other autoimmune phenomena, HLA associated genetic predisposition, and association with viral infection. A preceeding viral infection has been associated with the development of both GVHD and Sjogren's syndrome in clinical and experimental studies. Preliminary studies have shown that GVHD in the salivary and lacrimal glands and other tissues of the rat BMT model closely parallel GVHD in the human. In order to further develop GVHD in the salivary and lacrimal glands of the bone marrow transplanted rat as a model for Sjogren's syndrome, the link of viral infection to salivary and lacrimal gland GVHD will be studied.
The specific aims of this project are: 1) To infect rat salivary and lacrimal glands with the coronavirus Sialodacryoadenitis virus (SDAV) and to cause the development of GVHD in these tissues; 2) To examine the infected tissues and other head and neck tissues for histological evidence of SDAV infection and/or GVHD; 3) To correlate the pattern and timing of the viral infection with the onset of GVHD in the infected and distant tissues using light microscopy and immunofluorescent techniques.