Chronic graft-versus-host disease (GVHD) is a frequently debilitating and often fatal complication in recipients of allogeneic bone marrow. It displays many features of autoimmune diseases such as scleroderma, Sjogren's syndrome, and primary biliary cirrhosis. Although many immune abnormalities have been associated with chronic GVHD, the pathogenesis remains unknown. Spontaneous and rapidly induced chronic GVHD in the rat radiation chimera are clinically and histologically distinct from acute GVHD but very similar to chronic GVHD in humans. Using these multiple models, we have begun making progress towards understanding chronic GVHD. Cellular immunopathology studies with monoclonal antibodies show that the target tissues (skin and liver) have a predominance of helper phenotype cells (W3/25). In contrast with acute GVHD, these tissues have a predominance of nonhelper phenotype T lymphocytes (OX8). Within the skin, the helper phenotype cells with chronic GVHD are within the dermis, whereas with acute GVHD the epidermis is infiltrated with nonhelper (OX8+) cells. By comparing the immune abnormalities of the multiple models of chronic GVHD, we have been able to separate some inconsistently present abnormalities from other abnormalities present in all models. Thus, cutaneous IgM deposits and vasculitis appear to be unnecessary paraphenomena, while thymic medullary changes and nonspecific suppressor cells might be pathogenetically important. Current studies are concentrating on defining the necessary antigen discrepancy and tissue location of antigen disparity, the necessary lymphocyte populations, and the relative roles of immune deficiency versus direct immune injury in producing chronic GVHD. (TT)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028701-09
Application #
3168278
Study Section
Experimental Immunology Study Section (EI)
Project Start
1980-06-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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