SummaryA novel mechanism for breaking T cell self tolerance is described . B cells induced to make autoantibody by immunization ofmice with the non-self protein human cytochrome c can present the selfprotein mouse cytochrome c to autoreactive T cells in immunogenic form . This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen .

A new fungal immunomodulatory protein (Fip) has been purified from the edible mushroom, Volvariella volvacea, and designated Fip-vvo. Analysis of the purified protein by SDS/PAGE followed by Coomassie Blue staining demonstrated that Fip-vvo is a single polypeptide with an apparent molecular mass of 15 kDa. Periodic acid/Schiff staining showed that this single polypeptide lacks carbohydrates. Using an in vitro bioassay measuring blast-formation stimulatory activity, Fip-vvo was shown to stimulate the maximum proliferation of human peripheral blood lymphocytes at a concentration of 5 microg/ml. Fip-vvo was capable of agglutinating rat red blood cells. Neither haemagglutination nor mitogenic activities were inhibited by mono- or dimeric sugars. In vivo, repeat administration of Fip-vvo greatly reduced the production of BSA-induced Arthus reaction in mice, whereas little effect was observed on the prevention of systemic anaphylaxis reactions. The selectively enhanced transcriptional expression of interleukin (IL)-2, IL-4, interferon-gamma, tumour necrosis factor-alpha, lymphotoxin and IL-2 receptor by Fip-vvo was also demonstrated by reverse transcriptase-PCR. This finding suggests that Fip-vvo exerts its immunomodulatory effects via cytokine regulation. In addition, the complete amino acid sequence of Fip-vvo was obtained by direct protein sequencing. This protein consists of 112 amino acid residues with a blocked N-terminal end and has a calculated molecular mass of 12667 Da not including the N-terminal blocking group. By gel filtration analysis, Fip-vvo exhibited a molecular mass of 26 kDa for the native molecules in PBS. This result indicates that native Fip-vvo is most likely a non-covalently associated homodimeric molecule.

A new fungal immunomodulatory protein (FIP-fve) has been isolated and purified from the edible golden needle mushroom (Flammulina velutipes). The apparent molecular mass of FIP-fve determined by SDS/PAGE agrees well with the value of 12704 Da calculated from its amino acid composition and sequence. The complete amino acid sequence of FIP-fve was elucidated by protein sequencing techniques. FIP-fve consists of 114 amino acid residues with an acetylated amino end, and lacks methionine, half-cystine and histidine residues. FIP-fve was able to hemagglutinate human red blood cells. The immunomodulatory activity of FIP-fve was demonstrated by its stimulatory activity toward human peripheral blood lymphocytes, and its suppression of systemic anaphylaxis reactions and local swelling of mouse footpads. FIP-fve was found to enhance the transcriptional expression of interleukin-2 and interferon-gamma.

Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-γ in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-β plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-β Abs. IL-10 and TGF-β are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-β in cancer-mediated immunosuppression.

A new fungal immunomodulatory protein (FIP-fie) has been isolated and purified from the edible golden needle mushroom (Flammulina velutipes). The apparent molecular mass of FIP-fie determined by SDS/PAGE agrees well with the value of 12704 Da calculated from its amino acid composition and sequence. The complete amino acid sequence of FIP-fie was elucidated by protein sequencing techniques. FIP-fie consists of 114 amino acid residues with an acetylated amino end, and lacks methionine, halfcystine and histidine residues. FIP-fie was able to hemagglutinate human red blood cells. The immunomodulatory activity of FIP-fie was demonstrated by its stimulatory activity toward human peripheral blood lymphocytes, and its suppression of systemic anaphylaxis reactions and local swelling of mouse footpads. FIP-fie was found to enhance the transcriptional expression of interleukin-2 and interferon-y. Keywords. Flarnmulina velutipesGolden needle mushrooms (Flammulina velutipes) are a popular edible mushroom in Asia. We previously reported the isolation of a cardiotoxin, flammutoxin, from this mushroom [l]. Many polysaccharide biological response modifiers with antitumor activities, such as lentinan [2, 31 Schizophyllan [4] and OK-432 [5], have been isolated from fungi or bacteria. An anticarcinogenic and immunomodulatory protein has also been isolated from the edible grass mushroom, Volvariella volvacea [6]. Another fungal immunomodulatory protein (FIP), Ling Zhi-8, was isolated from the mycelia of Ganoderma. lucidum [7]. In this study, we describe the isolation and characterization of FIP-fie from the edible golden needle mushroom, E velutipes. The immunomodulatory and hemagglutinating activities of this FIP were studied, and the mechanism of immunornodulatory activity was examined. The complete amino acid sequence was determined by protein sequencing techniques. MATERIALS AND METHODSIsolation of FIP-fie. The fruit bodies of E velutipes (400 g) were homogenized with 1 1 ice-cold 5% acetic acid in the presence of 0.05 M 2-mercaptoethanol [6], and soluble proteins in the supernatant were precipitated by addition of ammonium sul-Correspondence to J. Y. Lin, Abbreviations. FIP-fie, fungal immunomodulatory protein isolated from Flammulina velutipes; IL-2, interleukin-2 ; IFN-y, interferon-y ; RT, reverse transcriptase.

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We demonstrated for the first time that food allergy can be induced by allergen exposure through the skin. Our results identify a novel role of EC sensitization in the pathogenesis of food allergy.

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