Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches

Thomas W. Spahn, Adriano Fontana, Ana M.C. Faria, Anthony J. Slavin, Hans Pietro Eugster, Xingmin Zhang, Pandelakis Koni, Nancy H. Ruddle, Richard A. Flavell, Paul D. Rennert, Howard L. Weiner

Research output: Contribution to journalArticle

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Abstract

Systemic hyporesponsiveness occurs following oral administration of antigen (oral tolerance) and involves the uptake and processing of antigen by the gut-associated lymphoid tissue (GALT), which includes Peyer's patches (PP) lamina propria lymphocytes and mesenteric lymph nodes (MLN). Animals with targeted mutations of genes in the tumor necrosis factor (TNF) family have differential defects in the development of peripheral lymphoid organs including PP and MLN, and provide a unique opportunity to investigate the role of GALT structures in the induction of oral tolerance. Oral tolerance could not be induced in TNF/lymphotoxin (LT) α-/- mice, which are devoid of both PP and MLN, although these animals could be tolerized by intraperitoneal administration of antigen, demonstrating the requirement for GALT for oral tolerance induction. LTβ-/- mice and LTα/LTβ+/- animals do not have PP but could be orally tolerized, as measured by IFN-γ production and delayed-type hypersensitivity responses by administration of both low or high doses of ovalbumin. To further investigate the requirement for PP, we tested the progeny of LTβ-receptor-IgG-fusion-protein (LTβRigG)-treated mice, which do not form PP but have an otherwise intact immune system. Although these animals had decreased fecal IgA production, they could be orally tolerized. Our results demonstrate that PP are not an absolute requirement for the induction of either high- or low-dose oral tolerance, although oral tolerance could not be induced in animals devoid of both PP and MLN.

Original languageEnglish (US)
Pages (from-to)1278-1287
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number4
DOIs
StatePublished - May 2 2001

Fingerprint

Peyer's Patches
Cellular Immunity
Lymphotoxin-alpha
Lymphoid Tissue
Lymph Nodes
Tumor Necrosis Factor-alpha
IgG Receptors
Antigens
Ovalbumin
Antigen Presentation
Delayed Hypersensitivity
Immunoglobulin A
Oral Administration
Immune System
Mucous Membrane
Lymphocytes
Mutation

Keywords

  • Knockout
  • Lymph node
  • Suppression
  • Tolerance
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Spahn, T. W., Fontana, A., Faria, A. M. C., Slavin, A. J., Eugster, H. P., Zhang, X., ... Weiner, H. L. (2001). Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. European Journal of Immunology, 31(4), 1278-1287. https://doi.org/10.1002/1521-4141(200104)31:4<1278::AID-IMMU1278>3.0.CO;2-A

Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. / Spahn, Thomas W.; Fontana, Adriano; Faria, Ana M.C.; Slavin, Anthony J.; Eugster, Hans Pietro; Zhang, Xingmin; Koni, Pandelakis; Ruddle, Nancy H.; Flavell, Richard A.; Rennert, Paul D.; Weiner, Howard L.

In: European Journal of Immunology, Vol. 31, No. 4, 02.05.2001, p. 1278-1287.

Research output: Contribution to journalArticle

Spahn, TW, Fontana, A, Faria, AMC, Slavin, AJ, Eugster, HP, Zhang, X, Koni, P, Ruddle, NH, Flavell, RA, Rennert, PD & Weiner, HL 2001, 'Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches', European Journal of Immunology, vol. 31, no. 4, pp. 1278-1287. https://doi.org/10.1002/1521-4141(200104)31:4<1278::AID-IMMU1278>3.0.CO;2-A
Spahn, Thomas W. ; Fontana, Adriano ; Faria, Ana M.C. ; Slavin, Anthony J. ; Eugster, Hans Pietro ; Zhang, Xingmin ; Koni, Pandelakis ; Ruddle, Nancy H. ; Flavell, Richard A. ; Rennert, Paul D. ; Weiner, Howard L. / Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. In: European Journal of Immunology. 2001 ; Vol. 31, No. 4. pp. 1278-1287.
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