Abstract
The local IgA response is a result of two related events, the induction of sensitized T and B cells in gut- or b ronchial-associated lymphoreticular tissues (GALT or BALT) and the final differentiation of IgA plasma cells in mucosal tissues where IgA is produced and transported to become secretory IgA (S-IgA) antibodies into external secretions. Oral administration of various types of antigens/vaccines may result in two types of response, i.e., S-IgA antibodies at mucosa and systemic unresponsiveness to antigen, a state termed oral tolerance. Regulatory T cells in GALT help account for both S-IgA responses and oral tolerance and thus serve to fine tune responses to orally encountered antigens. Studies in animal models and humans have shown that oral administration of antigens sensitize lymphoid cells in GALT which subsequently home to mucosa and result in S-IgA responses in several external secretions. The significant promise of oral vaccines for prevention of microbial diseases including neisserial diseases is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bockman, D. E. & M. D. Cooper (1973) Pinocytosis by epithelium associated with lymphoid follicles in the bursa of Fabricius, appendix and Peyer's patches. An electron microscopic study. Amer. J. Anat. 136: 455–478
Bockman, D. E., W. R. Boydston & D. H. Beezhold (1983) The role of epitherial cells in gut-associated immune reactivity. Ann. N.Y. Acad. Sci. 409: 129–143
Challacombe, S. J. & T. B. TomasiJr (1980) Systemic tolerance and secretory immunity after oral immunization. J. Exp. Med. 152: 1459–1472
Craig, S. W. & J. J. Cebra (1971) Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J. Exp. Med. 134: 188–200
Delacroix, D. L., G. N. Malburny & J. P. Vaerman (1985) Hepatobiliary transport of plasma IgA in the mouse: contribution to clearance of intravascular IgA. Eur. J. Immunol. 15: 893–899
Kiyono, H., J. L. Babb, S. M. Michalek & J. R. McGhee (1980) Cellular basis for elevated IgA responses in C3H/HeJ mice. J. Immunol. 125: 732–737
Kiyono, H., M. D. Cooper, J. F. Kearney, L. M. Mosteller, S. M. Michalek, W. J. Koopman & J. R. McGhee (1984) Isotype specificity of helper T cell clones. Peyer's patch Th cells preferentially collaborate with mature IgA B cells for IgA responses. J. Exp. Med. 159: 798–811
Kiyono, H., J. R. McGhee, L. M. Mosteller, J. H. Eldridge, W. J. Koopman, J. F. Kearney & S. M. Michalek (1982a) Murine Peyer's patch T cell clones. Characterization of antigen specific helper T cells for immunoglobulin A. J. Exp. Med. 156: 798–811
Kiyono, H., J. R. McGhee, M. J. Wannemuehler & S. M. Michalek (1982b) Lack of oral tolerance in C3H/HeJ mice. J. Exp. Med. 155: 605–610
Kiyono, H., L. M. Mosteller-Barnum, A. M. Pitts, S. J. Williamson, S. M. Michalek & J. R. McGhee (1985) Isotype-specific immunoregulation, IgA binding factors produced by Fcα receptor positive T cell hybridomas regulate IgA responses. J. Exp. Med. 161: 731–747
Kurita, T., H. Kiyono, K. Komiyama, C. E. Grossi, J. Mestecky & J. R. McGhee (1986). Isotype-specific immunoregulation: characterization and function of Fc receptors on T-T hybridomas which produce murine IgA binding factor. J. Immunol. 136: 3953–3960
Lycke, N., L. Lindholm & J. Holmgren (1985) Cholera antibody production in vitro by peripheral blood lymphocytes following oral immunization of humans and mice. Clin. Exp. Immunol. 62: 39–47
Mestecky, J. & J. R. McGhee (1987) Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Advan. Immunol. 40: 153–245
Mestecky, J., C. Czerkinsky, T. A. Brown, S. J. Prince, S. M. Michalek, M. W. Russell, S. Jackson, M. Scholler & J. R. McGhee (1986) Human immune responses to Streptococcus mutants. In: S. Hamada et al. (Eds) Molecular Microbiology and Immunobiology of Streptococcus mutants (pp. 297–306). Elsevier Scientific Publishers, Amsterdam
Mestecky, J., J. R. McGhee, R. R. Arnold, S. M. Michalek, S. J. Prince & J. L. Babb (1978) Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J. Clin. Invest. 61: 731–737
Owen, R. L. (1977) Sequential uptake of horseradish peroxidase by lymphoid follicle epithelium of Peyer's patches in the normal unobstructed mouse intestine: an ultrastructual study. Gastroenterology 72: 440–451
Owen, R. L. & A. L. Jones (1974) Epithelial cell specialization within human Peyer's patches: an ultrastructural study of intestinal lymphoid follicles. Gastroenterology 66: 189–203
Tomasi, T. B.Jr (1980) Oral tolerance — A review. Transplantation 79: 353–356
Suzuki, I., K. Kitamura, H. Kiyono, T. Kurita, D. R. Green & J. R. McGhee (1986b). Isotype-specific immunoregulation. Evidence for a distinct subset of T contrasuppressor cells for IgA responses in Murine Peyer's patches. J. Exp. Med. 164: 501–516
Suzuki, I., H. Kiyono, K. Kitamura, D. R. Green & J. R. McGhee (1986a) Abrogation of oral tolerance by contrasuppressor T cells suggests the presence of regulatory T cell networks in the mucosal immune system. Nature 320: 451–454
Weisz-Carrington, P., M. E. Roux, M. McWilliams, J. M. Phillips-Quagliata & M. E. Lamm (1979) Organ and isotype distribution of plasma cells producing specific antibody after oral administration: evidence for a generalized secretory immune system. J. Immunol. 123: 1705–1708
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McGhee, J.R., Kiyono, H., Michalek, S.M. et al. Enteric immunization reveals a T cell network for IgA responses and suggests that humans possess a common mucosal immune system. Antonie van Leeuwenhoek 53, 537–543 (1987). https://doi.org/10.1007/BF00415514
Issue Date:
DOI: https://doi.org/10.1007/BF00415514