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* Department of Microbiology and
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;
Department of Microbiology and Immunology and Department of Oral Biology, University at Buffalo, State University of New York, Buffalo, NY 14214;
Department of Microbiology and Immunology, Charles University, Prague, Czech Republic
Mucosal administration of Ags induces specific Abs in external secretions and systemic unresponsiveness termed oral or mucosal tolerance. The dominant response depends on the species studied, the nature, dose, frequency, route of Ag application, and the use of adjuvants. The temporal sequence of Ag exposure determines the quality of the ensuing immune response; although initial mucosal Ag exposure results in systemic T cell hyporesponsiveness, pre-existing systemic responses are refractory to the tolerizing effects of mucosal Ag encounter. Mucosal and systemic humoral responses may be induced concomitantly with diminished systemic T cell responses, thereby permitting Ab-mediated containment of mucosal Ags without stimulation of the systemic immune compartment. B cell Ig isotype switching and differentiation toward IgA production share common regulatory mechanisms with the suppression of T cells. Optimization of mucosal vaccination strategies has the potential for enhancing protective immune responses and suppressing systemic responses to autoantigens desirable for the treatment of autoimmune diseases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Institutes of Health Grants U19 AI28147, DE06746, DK071176, DK060132, and Czech Government Grants VZ MSM 0021 62081 and KJ 586206106.
2 Address correspondence and reprint requests to Dr. Jiri Mestecky, University of Alabama at Birmingham, Department of Microbiology, Box 1, 845 19th Street South, Birmingham, AL 35294-2170. E-mail address: mestecky{at}uab.edu
3 Abbreviations used in this paper: DTH, delayed-type hypersensitivity; CT, cholera toxin; CTB, cholera toxin B; KLH, keyhole limpet hemocyanin; LT, labile toxin; pIgA, polymeric IgA.
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