PubMed · 11218337
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2001-02-02. BCG in immunization programmes.. https://pubmed.ncbi.nlm.nih.gov/11218337/
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There is a rapidly expanding interest into the glutathione S-transferases (GSTs) and the structurally related molecules. Many of the latter have been identified as members of conserved protein families sharing structural and some times functional properties being particularly involved in heat-shock response, drug resistance and carcinogenesis. Also, evidence is emerging that members of the GST super family from some pathogens could exert immunomodulatory functions toward the cell of the immune system, involving separate profiles of cytokine gene transcription and different patterns of cell growth, illustrating therefore the 'one gene-dual function' phenomenon. The implication of these biological properties for pathogenesis is discussed.
Both nasal and oral administration of soluble protein antigens (Ags) induce tolerance, a phenomenon that has hampered mucosal vaccine design. To produce active immunity the use of adjuvants co-administered with soluble Ags is required. Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) were found to be powerful mucosal adjuvants, but they are not suitable for clinical use because of their associated toxicity. Therefore, there is the need to develop alternative strategies to deliver Ag in order to induce immunoprotection. Among these innovative tools, a new toxin, Zonula occludens toxin (Zot), produced by phages in toxigenic strains of Vibrio cholerae, has been recently exploited for its adjuvant activity at the mucosal level. The present study was undertaken to further highlight the adjuvant properties of Zot. The ability of Zot to induce a mucosal response to gliadin was demonstrated per serum antibody production. In our established model of systemic tolerance to gliadin, induced by its nasal administration, we found a reduced production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) upon administration of gliadin alone. This immune suppression was reverted in mice receiving gliadin together with Zot. As previously shown, the down-regulation of Th1-like cytokines was found to be associated to a suppression of the T-cell proliferation, while such a suppression was completely reverted by Zot co-administration. In conclusion, these data confirm Zot as a good mucosal adjuvant, considering its ability to interfere with the suppression of specific cell mediated immunity, probably as a result of the increased dose and/or altered processing of Ag at mucosal level.