Transepithelial immunomodulation by cholera toxin and non-toxic derivatives.
ABSTRACT Comparative analyses of murine dendritic cells (DC) isolated from the skin and from the intestinal mucosa after exposure to cholera toxin and its non-toxic B subunit disclose striking differences regarding the migratory and functional behaviour of these cells. The nature of the epithelial microenvironment, especially locally produced cytokines and chemokines, appears to influence the functional ability of skin and mucosal DCs to convey immunogenic as opposed to tolerogenic signals and hence to regulate immune responsiveness at skin and at mucosal sites.
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ABSTRACT: The mucosal immune system of mammals consists of an integrated network of lymphoid cells which work in concert with innate host factors to promote host defense. Major mucosal effector immune mechanisms include secretory antibodies, largely of immunoglobulin A (IgA) isotype, cytotoxic T cells, as well as cytokines, chemokines and their receptors. Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination or natural immunization by a mucosal route can effectively induce immune suppression. The diverse compartments located in the aerodigestive and genitourinary tracts and exocrine glands communicate via preferential homing of lymphocytes and antigen-presenting cells. Mucosal administration of antigens may result in the concomitant expression of secretory immunoglobulin A (S-IgA) antibody responses in various mucosal tissues and secretions, and under certain conditions, in the suppression of immune responses. Thus, developing formulations based on efficient delivery of selected antigens/tolerogens, cytokines and adjuvants may impact on the design of future vaccines and of specific immunotherapeutic approaches against diseases associated with untoward immune responses, such as autoimmune disorders, allergic reactions, and tissue-damaging inflammatory reactions triggered by persistent microorganisms.Immunological Reviews 09/1999; 170:197-222. · 12.16 Impact Factor