EXPRESSION OF THE OX40/GP34 SYSTEM IN CUTANEOUS GRAFT VERSUS HOST DISEASE

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The OX40 receptor and gp34 ligand system is a recently characterized receptor/ligand pair. First identified on activated rat CD4+ cells, OX40 has been demonstrated to be a 50kD cell surface glycoprotein whose expression in human blood seems to be limited to activated T-cells. Human OX40 is a member of the nerve growth factor receptor/tumor necrosis factor family whose members also include fas/APO-1, CD40, CD27, CD30, and 4-1BB/ILA antigens. These molecules are involved with regulation of cell growth, differentiation and apoptosis. Gp34 was recently discovered to be the ligand for human OX40. It is a type II membrane glycoprotein expressed on HTLV-1 infected T-cell lines. Gp34 is also expressed on EBV-infected B-cells, activated peripheral circulating B-cells, and it appears to mediate binding of activated T- cells to human dermal microvascular endothelial cells. The exact function of this receptor/ligand pair is unclear. However, recent studies have shown that in addition to cell adhesion, OX40/gp34 crosslinking results in propagation of T-cell proliferation, B-cell proliferation and differentiation into antibody producing plasma cells, and an alteration in cytokine secretion. The goal of this proposed investigation is to characterize the distribution of this receptor/ligand pair in murine and human skin and to determine its role in the pathogenesis of cutaneous graft versus host disease (GvHD).