Specialized roles for the pro-inflammatory cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) were characterized in TNF/LTα(-/-) and TNF(-/-) mice established by direct gene targeting of C57BL/6 ES cells. The requirement for LT early in lymphoid tissue organogenesis is shown to be distinct from the more subtle and varied role of TNF in promoting correct microarchitectural organization of leukocytes in LN and spleen. Development of normal Peyer's patch (PP) structure, in contrast, is substantially dependent on TNF. Only mice lacking LT exhibit retarded B cell maturation in vivo and serum immunoglobulin deficiencies. A temporal hierarchy in lymphoid tissue development can now be defined, with LT being an essential participant in general lymphoid tissue organogenesis, developmentally preceeding TNF that has a more varied and subtle role in promotion of correct spatial organization of leukocytes in LN and spleen. PP development in TNF(-/-) mice is unusual, indicating that TNF is a more critical participant for this structure than it is for other lymphoid tissues.

Item Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Immunology
Research Field:	Immunology not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Korner, H (Professor Heinrich Korner)
ID Code:	72429
Year Published:	1997
Web of Science® Times Cited:	259
Deposited By:	Research Division
Deposited On:	2011-08-26
Last Modified:	2011-08-29
Downloads:	0