EXPRESSION OF AN ADENOVIRALLY ENCODED LYMPHOTOXIN-BETA INHIBITOR PREVENTS CLEARANCE OF LISTERIA-MONOCYTOGENES IN MICE

The lymphotoxin (LT)-beta heterotrimer was recently identified as a mo lecule containing LT-alpha subunits, tethered to the cell through non- covalent association with an integral plasma membrane protein, derived from the LT-beta gene. Since knockout mutations of the LT-alpha gene yield animals that lack lymph nodes, whereas animals lacking either or both of the receptors for tumor necrosis factor (TNF) and LT-alpha ho motrimers have normal lymph nodes, it has been inferred that the assoc iation between the LT-beta heterotrimer and its cognate receptor is re quired for lymph node ontogeny. Similarly, LT-beta and its receptor ar e thought to be important for development of the spleen. Since LT-alph a deficient mice lack lymph nodes, it is difficult to assess the extra developmental contribution of LT-beta to immune competence. To this e nd we employed a strategy for the conditional blockade of LT-beta hete romer activity in normal mice. The interaction between LT-beta and its receptor is essential for the destruction of intracellular Listeria m onocytogenes. (C) 1995 Wiley-Liss, Inc.