CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DG) express OX40-ligand (OX40L) as has been: reported in humans. To understand how OX40 ligation affects differentiation of CD4 T ce lls at the time of priming, we constitutively expressed OX40L on DG using t he DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was t o a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately imm unized did not show marked CD4 T cell accumulation. The increased numbers o f CD4(+) CD62(low) cells in transgenic mice suggest that it: is activated C D4 T cells that accumulate within B cell follicles. These data are consiste nt with the notion that physiological engagement of OX40 (CD134) on activat ed CD4 T cells either initiates their migration into or causes them to be r etained in B follicles. In contrast, LPS-treated CD did not up-regulate OX4 0L expression. This dichotomy provides a molecular explanation of how DC mi ght integrate environmental and accessory signals to control cytokine diffe rentiation and migration in CD4 effector cells.