ABSTRACT
Tumor necrosis factor (TNFα) and lymphotoxin (LTα=TNFβ), originally characterized by their ability to induce tumor cell apoptosis and cachexia, are now considered to centrally mediate a broad range of biological activities. These activities encompass beneficial effects for the host in inflammation and in protective immune responses against a variety of infectious pathogens. TNF family members on the other hand also exert host damaging effects in sepsis, in tumor cachexia as well as in autoimmune diseases. In addition, the essential roles of LTα, LTβ, TNFα and their receptors during the organogenesis of secondary lymphoid organs and the maintenance of the architecture of lymphatic tissues now becomes widely recognized. The understanding of the biological functions of these cytokines and their specific cell surface receptors (TNFRp55, TNFRp75, and LTβR) has been crucially advanced by the study of gene-targeted mouse strains. This review focuses on the core members of the family of TNF receptors (TNFR) and TNF-like cytokines, on the role of TNFR and TNF-like cytokines in infection, sepsis and autoimmunity as well as on the pivotal involvement of these molecules in the development of secondary lymphoid organs and in the formation of germinal centers.
