The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells.

Abstract

SummaryFresh leukemic cells from patients with adult T cell leukemia (ATL) and some ATL-derived T cell hnes show adhesion to human umbilical vein endothelial cells (HUVECs) mainly through E-selectin, but a proportion of this binding remains unaffected by the addition of combinations of antibodies against known adhesion molecules. By immunizing mice with one of such cell hnes, we estabhshed monoclonal antibodies (mAbs), termed 131 and 315, that recognize a single cell surface antigen (Ag) and inhibit the remaining pathway of the adhesion. These mAbs did not react with normal resting peripheral blood mononuclear cells (PBMC) or most of the cell lines tested except for two other human T cell leukemia virus type I (HTLV-I)-infected T cell hnes. After stimulation with phytohemagglutinin (PHA), PBMC expressed Ag 131/315 transiently, indicating that these mAbs define a T cell activation Ag. Western blotting and immunoprecipitation revealed that Ag 131/315 has an apparent molecular mass of 50 kD. Expression cloning was done by transient expression in COS-7 cells and immunological selection to isolate a cDNA clone encoding Ag 131/315. Sequence analysis of the cDNA indicated that it is identical to human OX40, a member of the tumor necrosis factor/nerve growth factor receptor family. We then found that gp34, the hgand of OX40, was expressed on HUVECs and other types of vascular endothehal cells. Furthermore, it was shown that the adhesion ofCD4 + cells ofPHA-stimulated PBMC to unstimulated HUVECs was considerably inhibited by either 131 or 315. Finally, OX40 transfectants of Kit 225, a human interleukin 2-dependent T cell line, were bound specifically to gp34 transfectants of MMCE, a mouse epithelial cell hne, and this binding was blocked by either 315 or 5A8, an anti-gp34 mAb. These results indicate that the OX40/gp34 system directly mediates adhesion of activated T cells or OX40+-transformed T cells to vascular endothehal cells.

Microbial Compounds Selectively Induce Th1 Cell-Promoting or Th2 Cell-Promoting Dendritic Cells In Vitro with Diverse Th Cell-Polarizing Signals

“…Mouse anti-human mAbs were used against the following molecules: CD1a (OKT6; Ortho Diagnostic Systems, Beerse, Belgium), CD83 (HB15a, IgG2b; Immunotech, Marseille, France), CD86 (1G10, IgG2a; Innogenetics, Ghent, Belgium), HLA-DR (L234, IgG2a; BD Biosciences, San Jose, CA), and OX40L (5A8) (17). All mAbs were followed by FITC-conjugated goat F(abЈ) 2 anti-mouse IgG and IgM (Jackson ImmunoResearch Laboratories, West Grove, PA).…”

Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

“…How can this explain why OX40 blockade attenuates inflammatory diseases like experimental allergic encephalitis (EAE; reference 26) and hapten-induced colitis 27? The clue is that OX40L is expressed on vascular endothelium 28. The critical role of IL-12 but not IFN-γ in the generation of inflammatory CD4 cells has recently been highlighted 29.…”

Anti-tumour therapeutic efficacy of OX40L in murine tumour model

“…OX40 Ligand (OX40L) is a type II transmembrane protein and is expressed on B cells, dendritic cells (DCs) and endothelial cells (Stuber etal, 1995;Imura et al, 1996). Signals transmitted via CD28 and OX40 are highly synergistic for CD4 + T cell proliferation and survival , and interaction of OX40L with its receptor (CD134) has been shown to increase the expansion and survival of naïve CD4 + T cells, and to enhance memory Th cell survival by inhibiting peripheral deletion (Maxwell et al, 2000 J;Gramaglia et al, 2000).…”