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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 expressed membrane-bound TNF (memTNF(Delta/Delta) mice) were created by knocking-in the uncleavable Delta 1-9,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 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.

Pubmed ID: 11672536


  • Ruuls SR
  • Hoek RM
  • Ngo VN
  • McNeil T
  • Lucian LA
  • Janatpour MJ
  • K├Ârner H
  • Scheerens H
  • Hessel EM
  • Cyster JG
  • McEvoy LM
  • Sedgwick JD



Publication Data

October 23, 2001

Associated Grants


Mesh Terms

  • Animals
  • Apoptosis
  • Cells, Cultured
  • Chemokines
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Targeting
  • Germinal Center
  • Lipopolysaccharides
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Sequence Deletion
  • Shock
  • Spleen
  • Tumor Necrosis Factor-alpha