Biological functions of tumor necrosis factor cytokines and their receptors.

Tumor necrosis factor (TNF; formerly known as TNFalpha) and lymphotoxin (LT)alpha, originally characterized by their ability to induce tumor cell apoptosis and cachexia, are now considered as central mediators of 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 the core members of the TNF superfamily, LTalpha, LTbeta, TNF, and LIGHT as well as their receptors during the organogenesis of secondary lymphoid organs and the maintenance of the architecture of lymphatic tissues now becomes appreciated. The elucidation of the biological functions of these cytokines and their specific cell surface receptors has been crucially advanced by the study of gene-targeted mouse strains. This presentation summarizes the roles of TNFR and TNF-like cytokines in infection, sepsis and autoimmunity as well as the pivotal involvement of these molecules in the development of secondary lymphoid organs.