CYTOKINE MODULATION OF T-LYMPHOCYTE ACTIVATION BY INTESTINAL SMOOTH-MUSCLE CELLS

Background & Aims: Interleukin 1 beta (IL-beta) and tumor necrosis fac tor alpha (TNF-alpha) are present in the neuromuscular layers during i ntestinal inflammation and directly affect intestinal smooth Muscle fu nction. We investigated whether IL-1 beta and TNF-alpha modulate T-cel l activation by murine intestinal smooth muscle cells (ISMCs), Methods : alpha- and gamma-actin expression in ISMCs was confirmed using rever se-transcription polymerase chain reaction (FIT-PCR), ISMCs were analy zed for class II major histocompatibility complex (MHC), intercellular adhesion molecule 1 (ICAM-1), and B7 before and after exposure to int erferon gamma (IFN-gamma; 100 or 1000 U/mL) in the presence or absence of IL-1 beta (10 ng/mL) or TNF-alpha (5 ng/mL) for 72 hours. T-cell p roliferation on cytokine-pretreated ISMCs was measured in the absence or presence of anti-B7 antibodies, Results: In a dose-dependent fashio n, IFN-gamma-pretreated ISMCs expressed MHC class II, ICAM-1, and B7-2 , and simulated T-cell proliferation. Pretreatment of ISMCs with IL-1 beta and IFN-gamma reduced MHC class II acid ICAM-1 expression and inh ibited T-cell proliferation, When added with 100 U/mL IFN-gamma, TNF-a lpha enhanced MHC class II and ICAM-1 expression on ISMCs and T-cell p roliferation. However, TNF-alpha and 1000 U/mL IFN-gamma significantly decreased MHC class II expression and T-cell proliferation. Anti-B7-2 monoclonal antibody but not anti-B7-1 inhibited T-cell proliferative responses by >50%, Conclusions: Because IL-1 beta, TNF-alpha, and T ce lls are present in the intestinal muscle layers during inflammation, t hese cytokines may serve to modulate the activation of T cells in this site.