title: Chronic inflammation caused by lymphotoxin is lymphoid neogenesis.
abstract: In presenting a unifying concept for chronic inflammation and lymphoid organogenesis, we suggest that lymphotoxin's (LT, LT-alpha, TNF-beta) crucial role in these processes is pivotal and similar. Chronic inflammatory lesions that developed in the kidney and pancreas at the sites of transgene expression in rat insulin promoter-LT (RIP-LT) mice resembled lymph nodes with regard to cellular composition (T cells, B cells, plasma cells, and antigen-presenting cells), delineated T and B cell areas, primary and secondary follicles, characteristic morphologic and antigenic (ICAM-1, VCAM-1, MAdCAM-1, and PNAd) features of high endothelial venules, and ability to respond to antigen and undergo Ig class switching when obtained from mice immunized with SRBC. The vascular changes, with the exception of PNAd, appear to be the direct consequence of transgene derived LT expression, as they were also observed in RIP-LT mice lacking mature T and B cells. These data show that LT-induced chronic inflammation has the characteristics of organized lymphoid tissue.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kratz
authors.forename: A
authors.initials: A
authors.lastname: Campos-Neto
authors.forename: M S
authors.initials: MS
authors.lastname: Hanson
authors.forename: N H
authors.initials: NH
authors.lastname: Ruddle
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement; D002908:Chronic Disease; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D008221:Lymphoid Tissue / Q000254:growth & development*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009393:Nephritis / Q000209:etiology* / Q000276:immunology; D010195:Pancreatitis / Q000209:etiology* / Q000276:immunology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D007328:Insulin; D008233:Lymphotoxin-alpha; D011506:Proteins; C499308:Rag2 protein, mouse; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2