Expression of lymphotoxin-beta (LT-beta) in chronic inflammatory conditions.
Functional studies in gene-knockout and transgenic mice systems have shown that lymphotoxin-alpha and lymphotoxin-beta (LT-alpha and LT-beta) are of fundamental importance in peripheral lymphoid organ development, but it remains unclear what role these cytokines have to play in the adult immune response and in the pathogenesis of disease. In this study, a polyclonal anti-serum to human LT-beta was used to investigate the distribution of LT-beta by immunohistochemistry in normal and diseased tissues. In the gut, lymph nodes, spleen, and tonsil, there was some LT-beta present on a variety of lymphoid cell types. In contrast, strong staining for LT-beta was observed on plasma cells and a subpopulation of CD4+ T cells in tissues affected by chronic inflammatory disease or infection, for example in inflammatory bowel disease, and in lymph nodes obtained from patients with sarcoidosis and tuberculosis. In tuberculous and sarcoid lymph nodes, LT-beta expression also occurred on some but not all epithelioid histiocytes within granulomas and on multi-nucleated giant cells. These findings support a role for LT-beta in human disease and suggest that it might represent a therapeutic target in a variety of common infective or inflammatory disorders.
Agyekum
Sarah
S
Department of Infectious Diseases, Imperial College School of Medicine, Division of Investigative Science, Hammersmith Hospital, London W12 ONN, UK.
Church
Alison
A
Sohail
Muhammed
M
Krausz
Thomas
T
Van Noorden
Susan
S
Polak
Julia
J
Cohen
Jonathan
J
D000328:Adult; D000368:Aged; D015153:Blotting, Western / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000378:metabolism; D012507:Sarcoidosis / Q000378:metabolism*; D014376:Tuberculosis / Q000378:metabolism*
D007376:Interleukin-2; C505886:LTB protein, human; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D011994:Recombinant Proteins