Tumor Necrosis Factor/Tumor Necrosis Factor Receptor Family Members That Positively Regulate Immunity

The interactions between members of the tumor necrosis factor (TNF) family and their specific receptors (TNFRs) are influential in controlling cell division, life, and death. Recent evidence suggests that these interactions control the functionality and longevity of many types of cells involved in immune responses. In particular, it has become evident that certain interactions support the clonal expansion and survival of T-cells, B-cells, and dendritic cells and thus are essential for establishing a robust immune response. This review describes select TNF/TNFR family members that principally support activation and survival and prevent excessive cell death of T-cells (OX40L/OX40, 4-1BBL/4-1BB, CD30L/CD30, LIGHT/HVEM, CD70/CD27, and GITRL/GITR), B-cells (BAFF/BAFFR), and dendritic cells (RANKL/RANK). Expression of these ligands and receptors on the cell surface is highly regulated, and communication via them occurs during contact between T-cells and dendritic cells and between T-cells and B-cells.The functional dynamic between these TNF/TNFR members is slowly being unraveled, including whether these molecules act together or sequentially or control different type of immune responses. This review summarizes aspects of these TNF/TNFR interactions that are potentially important to immune responses.