MOLECULAR CHARACTERIZATION OF MURINE AND HUMAN OX40 OX40 LIGAND SYSTEMS - IDENTIFICATION OF A HUMAN OX40 LIGAND AS THE HTLV-1-REGULATED PROTEIN GP34/

A ligand was cloned for murine OX40, a member of the TNF receptor fami ly, using a T cell lymphoma cDNA library. The ligand (muOX40L) is a ty pe II membrane protein with significant identity to human gp34 (gp34), a protein whose expression on HTLV-1-infected human leukemic T cells is regulated by the tax gene. The predicted structures of muOX40L and gp34 are similar to, but more compact than, those of other ligands of the TNF family. Mapping of the muOX40L gene revealed tight linkage to gld, the FasL gene, on chromosome 1. gp34 maps to a homologous region in the human genome, 1q25. cDNAs for human OX40 receptor were cloned b y cross-hybridization with muOX40, and gp34 was found to bind the expr essed human receptor. Lymphoid expression of muOX40L was detected on a ctivated T cells, with higher levels found on CD4(+) rather than CD8() cells. The cell-bound recombinant ligands are biologically active, c o-stimulating T cell proliferation and cytokine production. Strong ind uction of IL-4 secretion by muOX40L suggests that this ligand may play a role in regulating immune responses. In addition, the HTLV-1 regula tion of gp34 suggests a possible connection between virally induced pa thogenesis and the OX40 system.