Immunity
Volume 15, Issue 4, October 2001, Pages 533-543
Journal home page for Immunity

Article
Membrane-Bound TNF Supports Secondary Lymphoid Organ Structure but Is Subservient to Secreted TNF in Driving Autoimmune Inflammation

https://doi.org/10.1016/S1074-7613(01)00215-1Get rights and content
Under an Elsevier user license
open archive

Abstract

Mice without secreted TNF but with functional, normally regulated and expressed membrane-bound TNF (memTNFΔ/Δ mice) were created by knocking-in the uncleavable Δ1-9,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 memTNFΔ/Δ mice relative to wild-type mice, and the nature of spinal cord infiltrates resembled that in TNF−/− mice. We conclude that memTNF supports many processes underlying lymphoid tissue structure, but secreted TNF is needed for optimal inflammatory lesion development.

Cited by (0)