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Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue
journal contributionposted on 2023-05-17, 07:43 authored by Heinrich KornerHeinrich Korner, Cook, M, Riminton, DS, Lemckert, FA, Hoek, RM, Ledermann, B, Kontgen, F, Fazekas de St Groth, B, Sedgwick, JD
Specialized roles for the pro-inflammatory cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) were characterized in TNF/LTÎ±(-/-) 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.
Publication titleEuropean Journal of Immunology
Department/SchoolMenzies Institute for Medical Research
PublisherWiley-V C H Verlag Gmbh
Place of publicationPo Box 10 11 61, Weinheim, Germany, D-69451