Ox-40 ligand: A potent costimulatory molecule for sustaining primary CD4 Tcell responses

Ox-40 and Ox-40 ligand (Ox-40L) are thought to be involved in T cell-APC in teractions. However, their exact role in T cell responses is undefined. Usi ng fibroblast transfectants expressing Ox-40L and/or B7-1, and CD4 cells fr om TCR transgenic mice, we investigated the effect of Ox-40 signaling on pr imary responses to the Ag pigeon cytochrome c. Ox-40 expression on naive CD 4 cells peaked 2 to 3 days after activation, and was lost by 4 to 5 days, A PCs with Ox-40L promoted partial activation of naive T cells with some IL-2 secretion, but were unable to enhance proliferation, unlike those with B7- 1, APCs coexpressing Ox-40L with B7-1 induced large quantities of IL-2 and promoted proliferative responses that persisted for several days. Effector cells taken 5 days after naive T cell activation reexpressed Ox-40 within 4 h and responded strongly to APCs expressing Ox-40L, whereas B7-1 had littl e effect. Synergy was also seen between Ox-40L and B7-1, with primarily IL- 2 being elevated, although IL-4 and IL-5 were also up-regulated, The most s triking action was on effector T cell proliferation, which continued at hig h levels for up to 4 days, with little proliferation evident at this time i n the absence of Ox-40 signals. These data suggest that Ox-40/Ox-40L intera ctions act after initial activation events to prolong clonal expansion and enhance effector cytokine secretion, and may he involved in promoting long- lived primary CD4 responses.