The autocrine role of tumor necrosis factor in the proliferation and functional differentiation of human lymphokine-activated T killer cells (T-LAK) in vitro

The autocrine role of tumor necrosis factor alpha (TNF) in the proliferation and functional differentiation of human lymphokine-activated T-killer cells (T-LAK) in vitro was investigated. Human peripheral blood lymphocytes initially stimulated with IL-2 and phytohemagglutinin-P (PHA) for 48 h will proliferate for long periods in vitro in the presence of IL-2. These T-LAK cells have been shown to be 95% CD3 positive. Employing ELISA techniques, greater than 500 pg/ml of TNF was found to be released in the supernatants of these cells during the first 5 days of culture. However, the levels dropped to 100-200 pg/ml by days 7-10. T-LAK cells grown from days 7 to 10 in the presence of IL-2 and rabbit anti-TNF were significantly growth inhibited (up to 23%). The cytolytic activity of T-LAK cells grown from days 0 to 7 in the presence of anti-TNF was also decreased (up to 75%). Phenotypic analysis of these anti-TNF treated T-LAK cells revealed a decrease in CD8 expression (up to 12%) and increase in CD4 expression (up to 27%) when compared with control cells. The data suggest that TNF has a regulatory role in the growth and functional differentiation of these human T-LAK cells

Immunoregulatory Mechanisms Underlying Prevention of Colitis-Associated Colorectal Cancer by Probiotic Bacteria

Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Probiotic bacteria produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anticarcinogenic effects. This study aimed to investigate the cellular and molecular mechanisms underlying the efficacy of probiotic bacteria in mouse models of cancer. Methodology/Principal Findings: The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in mouse models of inflammation-driven colorectal cancer. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Mice treated with CLA or VSL#3 recovered faster from the acute inflammatory phase of disease and had lower disease severity in the chronic, tumor-bearing phase of disease. Adenoma and adenocarcinoma formation was also diminished by both treatments. VSL#3 increased the mRNA expression of TNF-a, angiostatin and PPAR c whereas CLA decreased COX-2 levels. Moreover, VSL#3-treated mice had increased IL-17 expression in MLN CD4+ T cells and accumulation of Treg LPL and memory CD4+ T cells. Conclusions/Significance: Both CLA and VSL#3 suppressed colon carcinogenesis, although VSL#3 showed greater anticarcinogeni

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