Role of CD40 and B7 costimulators in inflammatory bowel diseases.
We analyse the costimulating role of CD40/CD40 ligand and B7/CD28 in inflammatory bowel diseases (IBD) as a potential target of antibody therapy. CD40, expressed by lamina propria B lymphocytes in gut mucosa, interacts with CD40 ligand on T cell. This interaction is implicated in the pathogenesis of IBD. In some animal models of colitis the anti-CD40L therapy demonstrated to be effective. Phase II trials on Crohn's disease are ongoing. B7.1 and B7.2, expressed by macrophages, interact with CD28, on T cell. B7.2 resulted implicated in ulcerative colitis, determining a Th2 pattern, whereas B7.1, a major Th1 stimulator, could be involved in Crohn's disease. In some animal models of colitis anti-B7.1, but not anti-B7.2, was effective. Anti B7 therapy was not yet tested in humans.
Polese
Lino
L
Dipartimento di Scienze Chirurgiche e Gastroenterologiche P.G. Cévese, Clinica Chirurgica I, Università di Padova, Italy. linopolese@hotmail.com
Angriman
Imerio
I
Scarpa
Marco
M
Norberto
Lorenzo
L
Sturniolo
Giacomo Carlo
GC
Cecchetto
Attilio
A
Ruffolo
Cesare
C
D'Amico
Davide Francesco
DF
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human