Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation

Mice without secreted TNF but with functional, normally regulated and expre ssed membrane-bound TNF (memTNF(Delta/Delta) mice) were created by knocking -in the uncleavable Delta1-9,K11E TNF allele. In contrast to TNF-deficient mice (TNF-/-), memTNF supported many features of lymphoid organ structure, except generation of primary B cell follicles. Splenic chemokine expression was near normal. MemTNF-induced apoptosis was mediated through both TNF-R1 and TNF-R2. That memTNF is suboptimal for development of inflammation was revealed in experimental autoimmune encephalomyelitis. Disease severity was reduced in memTNF(Delta/Delta) mice relative to wild-type mice, and the na ture of spinal cord infiltrates resembled that in TNF-/- mice. We conclude that memTNF supports many processes underlying lymphoid tissue structure, b ut secreted TNF is needed for optimal inflammatory lesion development.