Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation.
Immunity
; 15(4): 533-43, 2001 Oct.
Article
in En
| MEDLINE
| ID: mdl-11672536
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spleen
/
Tumor Necrosis Factor-alpha
/
Encephalomyelitis, Autoimmune, Experimental
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Year:
2001
Document type:
Article