Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-31T13:50:15.045Z Has data issue: false hasContentIssue false
  • English
  • Français

Regulation of mucosal immune responses in effector sites

Published online by Cambridge University Press:  28 February 2007

M. Bailey ,
F. J. Plunkett ,
H.-J. Rothkötter ,
M. A. Vega-Lopez ,
K. Haverson  and
C. R. Stokes
M. Bailey*
Affiliation:
Division of Molecular and Cellular Biology, Department of Clinical Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK
F. J. Plunkett
Affiliation:
Division of Molecular and Cellular Biology, Department of Clinical Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK
H.-J. Rothkötter
Affiliation:
Department of Functional Anatomy, Hannover Medical School, 4120 Carl-Neuberg Str., 30625 Hannover, Germany
M. A. Vega-Lopez
Affiliation:
CINVESTAV-IPN, Experimental Pathology Department, Av. IPN 2508, Mexico 07360 DF, Mexico
K. Haverson
Affiliation:
Division of Molecular and Cellular Biology, Department of Clinical Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK
C. R. Stokes
Affiliation:
Division of Molecular and Cellular Biology, Department of Clinical Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK
*
*Corresponding Author: Dr Mick Bailey, fax +44 117 928 9505, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In human disease and rodent models, immune responses in the intestinal mucosa can be damaging. Damage is characterised by villus atrophy, crypt hyperplasia and reduced ability to digest and absorb nutrients. In normal individuals active responses to harmless environmental antigens associated with food and commensal bacteria are controlled by the development of immunological tolerance. Similar pathological changes occur in piglets weaned early from their mothers. Active immune responses to food antigens are observed in these piglets, and we and others have hypothesised that the changes occur as a result of transient allergic immune responses to novel food or bacteria antigens. The normal mechanism for producing tolerance to food antigens may operate at induction (Peyer’s patches and mesenteric lymph nodes) or at the effector stage (intestinal lamina propria). In our piglet studies immunological tolerance occurs despite the initial active response. Together with evidence from rodents, this observation suggests that active responses are likely to be controlled at the effector stage, within the intestinal lamina propria. Support for this mechanism comes from the observation that human and pig intestinal T-cells are susceptible to apoptosis, and that this process is accelerated by antigen. We suggest that the role of the normal mature intestinal lamina propria is a balance between immunological effector and regulatory function. In neonatal animals this balance develops slowly and is dependant on contact with antigen. Immunological insults such as weaning may tip the balance of the developing mucosal immune system into excessive effector or regulatory function resulting in transient or chronic allergy or disease susceptibility.

Keywords

WeaningImmunityToleranceDevelopment
Type
Symposium on ‘Dietary influences on mucosal immunity’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 4 , November 2001 , pp. 427 - 435
Copyright
Copyright © The Nutrition Society 2001

References

Bailey, M, Clarke, CJ, Wilson, AD & Stokes, CR (1992) Depressed potential for interleukin-2 production following early weaning of piglets. Veterinary Immunology and Immunopathology 34, 197–207.CrossRefGoogle ScholarPubMed
Bailey, M, Hall, L, Bland, PW & Stokes, CR (1994 a) Production of cytokines by lymphocytes from spleen, mesenteric lymph node and intestinal lamina propria of pigs. Immunology 82, 577–583.Google ScholarPubMed
Bailey, M, Miller, BG, Telemo, E, Stokes, CR & Bourne, FJ (1993) Specific immunological unresponsiveness following active primary responses to proteins in the weaning diet of pigs. International Archives of Allergy and Immunology 101, 266–271.CrossRefGoogle Scholar
Bailey, M, Miller, BG, Telemo, E, Stokes, CR & Bourne, FJ (1994 b) Altered immune response to proteins fed after neonatal exposure of piglets to the antigen. International Archives of Allergy and Applied Immunology 103, 183–187.CrossRefGoogle Scholar
Bailey, M, Plunkett, F, Clarke, A, Sturgess, D, Haverson, K & Stokes, C (1998) Activation of T cells from the intestinal lamina propria of the pig. Scandinavian Journal of Immunology 48, 177–182.CrossRefGoogle ScholarPubMed
Barman, NN, Bianchi, ATJ, Zwart, RJ, Pabst, R & Rothkotter, HJ (1997) Jejunal and ileal Peyers patches in pigs differ in their postnatal development. Anatomy and Embryology 195, 41–50.CrossRefGoogle ScholarPubMed
Bianchi, AT, Zwart, RJ, Jeurissen, SH & Moonen-Leusen, HW (1992) Development of the B- and T-cell compartments in porcine lymphoid organs from birth to adult life: an immunohistological approach. Veterinary Immunology and Immunopathology 33, 201–221.CrossRefGoogle Scholar
Bland, PW & Warren, LG (1986) Antigen presentation by epithelial cells of the rat small intestine. I. Kinetics, antigen specificity and blocking by anti-ia antisera. Immunology 58, 1–7.Google ScholarPubMed
Boirivant, M, Fuss, I, Fiocchi, C, Klein, JS, Strong, SA & Strober, W (1996 a) Hypoproliferative human lamina propria T-cells retain the capacity to secrete lymphokines when stimulated via CD2/CD28 pathways. Proceedings of the Association of American Physicians 108, 55–67.Google ScholarPubMed
Boirivant, M, Pica, R, Demaria, R, Testi, R, Pallone, F & Strober, W (1996 b) Stimulated human lamina propria T-cells manifest enhanced FAS-mediated apoptosis. Journal of Clinical Investigation 98, 2616–2622.CrossRefGoogle ScholarPubMed
Braunstein, J, Qiao, L, Autschbach, F, Schurmann, G & Meuer, S (1997) T cells of the human intestinal lamina propria are high producers of interleukin-10. Gut 41, 215–220.CrossRefGoogle ScholarPubMed
Butler, JE, Sun, J, Weber, P, Navarro, P & Francis, D (2000) Antibody repertoire development in fetal and neonatal piglets. III. Colonisation of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues. Immunology 100, 119–130.CrossRefGoogle Scholar
Challacombe, SJ & Tomasi, B (1980) Systemic tolerance and secretory immunity after oral immunisation. Journal of Experimental Medicine 152, 1459–1472.CrossRefGoogle Scholar
Dreau, D, Lalles, JP, Philouzerome, V, Toullec, R & Salmon, H (1994) Local and systemic immune responses to soybean protein ingestion in early-weaned pigs. Journal of Animal Science 72, 2090–2098.CrossRefGoogle ScholarPubMed
Dreau, D, Lalles, JP, Toullec, R & Salmon, H (1995) B-lymphocyte and T-lymphocyte are enhanced in the gut of piglets fed heat-treated soybean proteins. Veterinary Immunology and Immunopathology 47, 69–79.CrossRefGoogle Scholar
Duchmann, R, Kaiser, I, Hermann, E, Mayet, W, Ewe, K & zum Buschenfelde, KHM (1995 a) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clinical and Experimental Immunology 102, 448–455.CrossRefGoogle ScholarPubMed
Duchmann, R, Kaiser, I, Hermann, E, Mayet, W, Ewe, K & zum Buschenfelde, KHM (1995 b) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clinical and Experimental Immunology 102, 448–455.CrossRefGoogle ScholarPubMed
Garside, P, Steel, M, Worthey, EA, Kewin, PJ, Howie, SEM, Harrison, DJ, Bishop, D & Mowat, AM (1996) Lymphocytes from orally tolerised mice display enhanced susceptibility to death by apoptosis when cultured in the absence of antigen in vitro. American Journal of Pathology 149, 1971–1979.Google Scholar
Gorelik, L & Flavell, RA (2000) Abrogation of TGFβ signalling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12, 171–181.CrossRefGoogle Scholar
Groux, H, O'Garra, A, Bigler, M, Rouleau, M, Antonenko, S, deVries, JE & Roncarolo, MG (1997) A CD4+ T-cell subset inhibits antigen-specific T cell responses and prevents colitis. Nature 389, 737–742.CrossRefGoogle ScholarPubMed
Halstensen, TS, Scott, H & Brandtzaeg, P (1990) Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45RO in celiac disease. European Journal of Immunology 20, 1825–1830.CrossRefGoogle ScholarPubMed
Hampson, DJ (1986) Alterations in piglet small intestinal structure at weaning. Research in Veterinary Science 40, 32–40.CrossRefGoogle ScholarPubMed
Harriman, GR, Hornqvist, E & Lycke, NY (1992) Antigen-specific and polyclonal CD4+ lamina propria T-cell lines – phenotypic and functional characterisation. Immunology 75, 66–73.Google Scholar
Hauer, AC, Bajaj-Elliott, M, Williams, CB, Walker-Smith, JA & MacDonald, TT (1998) An analysis of interferon gamma, IL-4, IL-5 and IL-10 production by elispot and quantitative reverse transcriptase pcr in human Peyers patches. Cytokine 10, 627–634.CrossRefGoogle Scholar
Haverson, K, Bailey, M & Stokes, CR (1999) T-cell populations in the pig intestinal lamina propria: memory cells with unusual phenotypic characteristics. Immunology 96, 66–73.CrossRefGoogle ScholarPubMed
Haverson, K, Saalmuller, A, Alvarez, B, Alonso, F, Bailey, M, Bianchi, ATJ, Boersma, WJA, Chen, Z, Davis, WC, Dominguez, J, Engelhardt, H, Ezquerra, A et al. (2001) Overview of the third international workshop on swine leucocyte differentiation antigens. Veterinary Immunology and Immunopathology 80, 5–23.CrossRefGoogle Scholar
Haverson, K, Singha, S, Stokes, CR & Bailey, M (2000) Professional and non-professional antigen-presenting cells in the porcine small intestine. Immunology 101, 1–13.CrossRefGoogle ScholarPubMed
Holt, PG, Yabuhara, A, Prescott, S, Venaille, T, Macaubas, C, Holt, BJ, Bjorksten, B & Sly, PD (1997) Allergen recognition in the origin of asthma. CIBA Foundation Symposium 206, 35–55.Google ScholarPubMed
Iqbal, N, Oliver, JR, McCabe, RP, Elson, CO & Weaver, CT (1999) B7-1 expression on intestinal epithelium prevents oral tolerance induction. FASEB Journal 13, A606.Google Scholar
James, SP, Kwan, WC & Sneller, MC (1990) T cells in the inductive and effector compartments of the intestinal mucosal immune system of nonhuman primates differ in lymphokine mRNA expression, lymphokine utilisation and regulatory function. Journal of Immunology 144, 1251–1256.CrossRefGoogle ScholarPubMed
Li, DF, Nelssen, JL, Reddy, PG, Blecha, F, Klemm, R & Goodband, RD (1991) Interrelationship between hypersensitivity to soybean proteins and growth performance in early-weaned pigs. Journal of Animal Science 69, 4062–4069.CrossRefGoogle ScholarPubMed
McCracken, BA, Spurlock, ME, Roos, MA, Zuckermann, FA & Gaskins, HR (1999) Weaning anorexia may contribute to local inflammation in the piglet small intestine. Journal of Nutrition 129, 613–619.CrossRefGoogle ScholarPubMed
MacDonald, TT & Ferguson, A (1976) Hypersensitivity reactions in the small intestine. 2. Effects of allograft rejection on mucosal architecture and lymphoid cell infiltrate. Gut 17, 81–89.CrossRefGoogle ScholarPubMed
Mayer, L & Shlien, R (1987) Evidence for function of Ia molecules on gut epithelial cells in man. Journal of Experimental Medicine 166, 1471–1483.CrossRefGoogle ScholarPubMed
Miller, BG, James, PS, Smith, MW & Bourne, FJ (1986) Effect of weaning on the capacity of the pig intestinal villi to digest and absorb nutrients. Journal of Agricultural Science, Cambridge 107, 579–589.CrossRefGoogle Scholar
Miller, GG, Whittemore, CT, Stokes, CR & Telemo, E (1994) The effect of delayed weaning on the development of oral tolerance to soya-bean protein in pigs. British Journal of Nutrition 71, 615–625.CrossRefGoogle ScholarPubMed
Mowat, AM & Ferguson, A (1981) Hypersensitivity in the small intestinal mucosa. V. induction of cell-mediated immunity to a dietary antigen. Clinical and Experimental Immunology 43, 574–582.Google ScholarPubMed
Mowat, AM & Ferguson, A (1982) Intraepithelial count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine. Gastroenterology 83, 417–423.CrossRefGoogle ScholarPubMed
Pabst, R, Geist, M, Rothkotter, HJ & Fritz, FJ (1988) Postnatal development and lymphocyte production of jejunal and ileal Peyers patches in normal and gnotobiotic pigs. Immunology 64, 539–544.Google ScholarPubMed
Pabst, R & Rothkotter, H-J (1999) Postnatal development of lymphocyte subsets in different compartments of the small intestine of pigs. Veterinary Immunology and Immunopathology 72, 167–173.CrossRefGoogle Scholar
Pescovitz, MD (1998) Immunology of the pig. In Handbook of Vertebrate Immunology, pp. 373–420 [Pastoret, P-P, Griebel, P, Bazin, H and Govaerts, A, editors] London: Academic Press.Google Scholar
Powrie, F, Carlino, J, Leach, MW, Mauze, S & Coffman, RL (1996) A critical role for transforming growth factor beta but not interleukin-4 in the suppression of T helper type 1-mediated colitis by CD45RB(low)CD4+ T cells. Journal of Experimental Medicine 183, 2669–2674.CrossRefGoogle Scholar
Rothkotter, HJ, Ulbrich, H & Pabst, R (1991) The postnatal development of gut lamina propria lymphocytes: number, prolif-eration and T and B cell subsets in conventional and germ-free pigs. Pediatric Research 29, 237–242.CrossRefGoogle Scholar
Santos, LMB, Al-Sabbagh, A, Londono, A & Weiner, HL (1994) Oral tolerance to myelin basic protein induces regulatory TGFβ-secreting T-cells in Peyers patches of SJL mice. Cellular Immunology 157, 439–447.CrossRefGoogle Scholar
Stokes, CR, Newby, TJ & Bourne, FJ (1983) The influence of oral immunisation on local and systemic immune responses to heterologous antigens. Clinical and Experimental Immunology 52, 399–406.Google ScholarPubMed
Sun, J, Hayward, C, Shinde, R, Christensen, R, Ford, SP & Butler, JE (1998) Antibody repertoire development in fetal and neonatal piglets. I. four VH genes account for 80 % of VH usage during 84 days of fetal life. Journal of Immunology 161, 5070–5078.CrossRefGoogle ScholarPubMed
Targan, SR, Deem, RL, Liu, M, Wang, S & Nel, A (1995) Definition of a lamina propria T-cell responsive state – enhanced cytokine responsiveness of T-cells stimulated through the CD2 pathway. Journal of Immunology 154, 664–675.CrossRefGoogle ScholarPubMed
Vega-Lopez, MA, Bailey, M, Telemo, E & Stokes, CR (1995) Effect of early weaning on the development of immune cells in the pig intestine. Veterinary Immunology and Immunopathology 44, 319–327.CrossRefGoogle Scholar
Vega-Lopez, MA, Telemo, E, Bailey, M, Stevens, K & Stokes, CR (1993) Immune cell distribution in the small intestine of the pig: immunohistological evidence for an organized compartmentalization in the lamina propria. Veterinary Immunology and Immunopathology 37, 49–60.CrossRefGoogle ScholarPubMed
Viney, JL & MacDonald, TT (1990) Selective death of T-cell receptor γ/δ intaepithelial lymphocytes by apoptosis. European Journal of Immunology 20, 2809–2812.CrossRefGoogle ScholarPubMed
Wattrang, E, Wallgren, P, Lindberg, A & Fossum, C (1998) Signs of infections and reduced immune functions at weaning of conventionally reared and specific pathogen free pigs. Journal of Veterinary Medicine 45B, 7–17.CrossRefGoogle Scholar
Wilson, AD, Haverson, K, Bland, PW, Stokes, CR & Bailey, M (1996) Expression of class II MHC antigens on normal pig intestinal endothelium. Immunology 88, 98–103.CrossRefGoogle ScholarPubMed
Wilson, AD, Stokes, CR & Bourne, FJ (1989) Effect of age on absorbtion and immune responses to weaning or introduction of novel dietary antigens in pigs. Research in Veterinary Science 46, 180–186.CrossRefGoogle ScholarPubMed
Zeitz, M, Green, WC, Peffer, NJ & James, SP (1988) Lymphocytes isolated from the intestinal lamina propria of normal non-human primates have increased expression of genes associated with T cell activation. Gastroenterology 94, 647–655.CrossRefGoogle Scholar