Colitis induced by enteric bacterial antigen-specific CD4+ T cells requires CD40-CD40 ligand interactions for a sustained increase in mucosal IL-12.

摘要: C3H/HeJBir is a mouse substrain that highly susceptible to colitis. Their CD4 + T cells react Ags of the commensal enteric bacteria, and latter can mediate colitis when activated by these transferred histocompatible scid recipients. In this study, multiple long-term cell (Bir) lines reactive bacterial have been generated. All were Ag specific, pauciclonal, Th1 predominant; most induced uniformly after transfer Lesions focal marked increased expression IL-12p40 IFN-γ mRNA protein. Pathogenic Bir expressed CD40 ligand (CD40L) cultured with Ag-pulsed APCs in vitro. Production IL-12 was also such cultures, an effect Ag- cell-dependent required costimulation CD40, but not B7. The two did induce lesions failed significantly express CD40L or increase APCs. Administration anti-CD40L blocked disease pathogenic cells. We conclude interactions colon mucosa between CD40L-expressing endogenously loaded are critical for sustained increases local production progression