Chronic GVHD is a major clinical problem in human recipients of bone marrow, which leads to autoantibody production, fibrosis, and skin pathology (Vogelsang, 2001). Animals undergoing cGVHD develop a SLE-like systemic autoimmune syndrome including production of antinuclear autoantibodies and immune complex-mediated renal disease (van Rappard-Van der Veen et al., 1984). The etiology may be attributed to the breakdown of tolerance of autoreactive T and B cells resulting from alloresponse to minor recipient histocompatibility antigens. There is a preponderance of evidence that indicates both alloreactive donor CD4+ T cells and autoreactive host CD4+ T cells are essential for cGVHD (Chen et al., 1998; Morris et al., 1990). Chronic GVHD can be induced by transfer of parental lymphocytes into F1 hybrid mice.
Kim et al. (2005) studied the role of CD137 agonist in cGVHD. cGVHD was induced by transfer of DBA/2 (H-2d) parental lymphocytes into BDF1 mice (H-2b/d). They found that single dose of agonistic anti-CD137 mAb (3H3) (Shuford et al. ,1997) injection was able to block the production of anti-DNA IgG and total IgE, abrogate immune complex deposition in kidney and prevent glomerulonephritis in the recipients, leading to increased survival. Additionally, such treatment also ameliorates advanced cGVHD.
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