Mesenchymal stem cells (MSC) have recently been used successfully in humans to control severe graft-versus-host disease. However, the mechanisms involved in their immunomodulatory effects remain a matter of debate. Here, we show that MSC are unable to activate allogeneic T cells even in the presence of T-cell growth factors. We then found that MSC inhibit T-cell proliferation triggered either by allogeneic, mitogenic or antigen-specific stimuli. Interestingly, MSC inhibit T-cell proliferation by inducing apoptosis of activated T cells, but have no effect on resting T cells. Furthermore, we show that this apoptosis could be related to the conversion of tryptophan into kynurenine by indoleamine 2,3-dioxygenase expressed by MSC in the presence of IFNc. Moreover, we show that the inhibitory effect of MSC is neither abrogated nor modified during expansion in culture or after irradiation. Together, these results bring new insight to the mechanisms of immunosuppression induced by MSC and might help to develop their clinical use controlling immune-related adverse effects in humans.

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The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated, perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2-0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs. The experimental zinc deficiency caused a slight decrease of superoxide dismutase activity, accompanied by increased production of peroxidated lipids. Ethanol administration appeared to increase the levels of peroxidated lipids in the heart. Finally, the combination of zinc deficiency and ethanol administration had very harmful effects, especially on lipid peroxidation and contractile function of the isolated, perfused heart in preischemic conditions.

Nine preruminant male calves were prepared surgically with lymphatico-venous shunts and/or re-entrant gallbladder to proximal duodenum shunts to evaluate the effects of degree of saturation of dietary fat on cholesterol transport in intestinal lymph and bile. Liquid diets were formulated to contain 12.5% dried skim milk (SM) or 10.5% SM to which 2% soybean oil (SBO), milk fat (MF), beef tallow (T) or one of these fats plus supplemental cholesterol was added. After 3-d dietary treatments, total lymph collections were made to determine flow rate, total lipid and cholesterol transport. Total bile collections were made to determine flow rate and cholesterol and bile acid transport. For SM, SBO, MF and T diets, respectively, average lipid transport in mesenteric lymph was 8.94, 32.58, 64.86 and 38.12 mg/(h X kg body weight), and cholesterol transport averaged 1.09, 1.92, 2.41 and 2.70 mg/(h X kg body weight). Lipid and cholesterol transport in lymph was less (P less than 0.05) in SM-fed calves than in fat-fed calves. Source of fat or supplemental cholesterol had no statistically significant effect on amount of cholesterol or bile acid transported in bile; however, calves fed SM transported greater quantities of cholesterol in bile than did calves fed fat or fat plus cholesterol.

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