Involvement of the Liver in the Induction of CD8 T Cell Tolerance towards Oral Antigen

 

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Zusammenfassung

Die Leber ist ein Organ mit einzigartigem immunregulatorischen Potenzial. In dieser Arbeit wird die experimentelle Evidenz dargestellt, die für die Beteiligung hepatischer Zellpopulationen an der Induktion von oraler Toleranz spricht. Obwohl die Induktion von Immuntoleranz gegenüber oralen Antigenen vor allem im lymphatischen Gewebe des Gastrointestinaltraktes erfolgt, besteht ein weiterer Bedarf für die Aufrechterhaltung peripherer Immuntoleranz außerhalb des Gastrointestinaltraktes, da orale Antigene innerhalb von Minuten nach Aufnahme schnell über den Blutstrom systemisch verteilt werden. Neben hepatischen dendritischen Zellen sind vor allem sinusoidale Endothelzellen der Leber an der Aufnahme von oralem Antigen aus portalvenösem Blut und der Kreuzpräsentation dieser Antigene auf MHC-I-Molekülen für CD8-T-Zellen beteiligt. Die Folge der Kreuzpräsentation oraler Antigene durch sinusoidale Endothelzellen der Leber ist die Induktion von CD8-T-Zell-Immuntoleranz. Diese Befunde unterstreichen die Bedeutung der Leber in der Aufrechterhaltung peripherer Immuntoleranz auch gegenüber oralen Antigenen.

Abstract

The liver is an organ with unique immune regulatory potential. This review highlights the experimental evidence for the involvement of hepatic cell populations in the induction of oral tolerance. Although immune tolerance towards oral antigens is mainly induced in the gastrointestinal tract within gut associated lymphatic tissue via generation of regulatory CD4 T cells, there is a further need for tolerance induction outside the gastrointestinal tract, because oral antigens rapidly distribute within minutes systemically through the blood stream. Besides hepatic dendritic cells, liver sinusoidal endothelial cells are active in the uptake and cross-presentation of oral antigens from portal venous blood and engage in the induction of CD8 T cell tolerance towards these antigens. These reports strengthen the notion that the liver participates in the induction of oral tolerance.

References

• 1 Cantor H, Dumont A. Hepatic suppression of sensitization to antigen absorbed into the portal system.  Nature. 1967;  44 744
  PubMedGoogle Scholar
• 2 Callery M P, Kamei T, Flye M W. The effect of portacaval shunt on delayed-hypersensitivity responses following antigen feeding.  J Surg Res. 1989;  44 391-394
  PubMedGoogle Scholar
• 3 Yang R, Liu Q, Grosfeld J L. et al . Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction.  J Pediatr Surg. 1994;  44 1145-1148
  PubMedGoogle Scholar
• 4 Calne R Y. Induction of immunological tolerance by porcine liver allografts.  Nature. 1969;  44 472-476
  PubMedGoogle Scholar
• 5 Dahmen U, Qian S, Rao A S. et al . Split tolerance induced by orthotopic liver transplantation in mice.  Transplantation. 1994;  44 1-8
  PubMedGoogle Scholar
• 6 Barker C F, Corriere J N Jr. Canine renal homotransplantation with venous drainage via the portal vein.  Ann Surg. 1967;  44 279-282
  PubMedGoogle Scholar
• 7 Boeckx W, Sobis H, Lacquet A. et al . Prolongation of allogeneic heart graft survival in the rat after implantation on portal vein.  Transplantation. 1975;  44 145-149
  PubMedGoogle Scholar
• 8 Gorczynski R M, Chan Z, Chung S. et al . Prolongation of rat small bowel or renal allograft survival by pretransplant transfusion and/or by varying the route of allograft venous drainage.  Transplantation. 1994;  44 816-820
  PubMedGoogle Scholar
• 9 Yu S, Nakafusa Y, Flye M W. Portal vein administration of donor cells promotes peripheral allospecific hyporesponsiveness and graft tolerance.  Surgery. 1994;  44 229-234; discussion 234 - 235
  PubMedGoogle Scholar
• 10 Bertolino P, Bowen D G, McCaughan G W. et al . Antigen-specific primary activation of CD8 + T cells within the liver.  J Immunol. 2001;  44 5430-5438
  PubMedGoogle Scholar
• 11 Bertolino P, McCaughan G W, Bowen D G. Role of primary intrahepatic T-cell activation in the “liver tolerance effect”.  Immunol Cell Biol. 2002;  44 84-92
  PubMedGoogle Scholar
• 12 Bowen D G, Zen M, Holz L. et al . The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.  J Clin Invest. 2004;  44 701-712
  PubMedGoogle Scholar
• 13 Richman L K, Klingenstein R J, Richman J A. et al . The murine Kupffer cell. I. Characterization of the cell serving accessory function in antigen-specific T cell proliferation.  J Immunol. 1979;  44 2602-2609
  PubMedGoogle Scholar
• 14 Rubinstein D, Roska A K, Lipsky P E. Antigen presentation by liver sinusoidal lining cells after antigen exposure in vivo.  J Immunol. 1987;  44 1377-1382
  PubMedGoogle Scholar
• 15 Knolle P, Schlaak J, Uhrig A. et al . Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge.  J Hepatol. 1995;  44 226-229
  PubMedGoogle Scholar
• 16 Bissell D M, Wang S S, Jarnagin W R. et al . Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation.  J Clin Invest. 1995;  44 447-455
  PubMedGoogle Scholar
• 17 Callery M P, Kamei T, Flye M W. Kupffer cell blockade inhibits induction of tolerance by the portal venous route.  Transplantation. 1989;  44 1092-1094
  PubMedGoogle Scholar
• 18 Kamei T, Callery M P, Flye M W. Kupffer cell blockade prevents induction of portal venous tolerance in rat cardiac allograft transplantation.  J Surg Res. 1990;  44 393-396
  PubMedGoogle Scholar
• 19 Steinman R M, Hawiger D, Liu K. et al . Dendritic cell function in vivo during the steady state: a role in peripheral tolerance.  Ann N Y Acad Sci. 2003;  44 15-25
  PubMedGoogle Scholar
• 20 Goddard S, Youster J, Morgan E. et al . Interleukin-10 secretion differentiates dendritic cells from human liver and skin.  Am J Pathol. 2004;  44 511-519
  PubMedGoogle Scholar
• 21 Jomantaite I, Dikopoulos N, Kroger A. et al . Hepatic dendritic cell subsets in the mouse.  Eur J Immunol. 2004;  44 355-365
  PubMedGoogle Scholar
• 22 Pillarisetty V G, Shah A B, Miller G. et al . Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition.  J Immunol. 2004;  44 1009-1017
  PubMedGoogle Scholar
• 23 Lau A H, Thomson A W. Dendritic cells and immune regulation in the liver.  Gut. 2003;  44 307-314
  PubMedGoogle Scholar
• 24 Matsuno K, Ezaki T, Kudo S. et al . A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph [see comments].  J Exp Med. 1996;  44 1865-1878
  PubMedGoogle Scholar
• 25 Kudo S, Matsuno K, Ezaki T. et al . A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation.  J Exp Med. 1997;  44 777-784
  PubMedGoogle Scholar
• 26 Steinbrink K, Wolfl M, Jonuleit H. et al . Induction of tolerance by IL-10-treated dendritic cells.  J Immunol. 1997;  44 4772-4780
  PubMedGoogle Scholar
• 27 Lutz M B, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?.  Trends Immunol. 2002;  44 445-449
  PubMedGoogle Scholar
• 28 Steinman R M, Hawiger D, Nussenzweig M C. Tolerogenic dendritic cells.  Annu Rev Immunol. 2003;  44 685-711
  PubMedGoogle Scholar
• 29 Smedsrod B. Clearance function of scavenger endothelial cells.  Comp Hepatol. 2004;  44 S22
  PubMedGoogle Scholar
• 30 Lohse A W, Knolle P A, Bilo K. et al . Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.  Gastroenterology. 1996;  44 1175-1181
  PubMedGoogle Scholar
• 31 Knolle P A, Schmitt E, Jin S. et al . Induction of cytokine production in naive CD4(+) T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 cells.  Gastroenterology. 1999;  44 1428-1440
  PubMedGoogle Scholar
• 32 Limmer A, Ohl J, Kurts C. et al . Efficient presentation of exogenous antigen by liver endothelial cells to CD8 + T cells results in antigen-specific T-cell tolerance.  Nat Med. 2000;  44 1348-1354
  PubMedGoogle Scholar
• 33 Rescigno M, Urbano M, Valzasina B. et al . Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria.  Nat Immunol. 2001;  44 361-367
  PubMedGoogle Scholar
• 34 Niess J H, Brand S, Gu X. et al . CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance.  Science. 2005;  44 254-258
  PubMedGoogle Scholar
• 35 Mowat A M. Anatomical basis of tolerance and immunity to intestinal antigens.  Nat Rev Immunol. 2003;  44 331-341
  PubMedGoogle Scholar
• 36 Karlsson M, Lundin S, Dahlgren U. et al . “Tolerosomes” are produced by intestinal epithelial cells.  Eur J Immunol. 2001;  44 2892-2900
  PubMedGoogle Scholar
• 37 Blanas E, Carbone F R, Allison J. et al . Induction of autoimmune diabetes by oral administration of autoantigen.  Science. 1996;  44 1707-1709
  PubMedGoogle Scholar
• 38 Hanninen A, Braakhuis A, Heath W R. et al . Mucosal antigen primes diabetogenic cytotoxic T-lymphocytes regardless of dose or delivery route.  Diabetes. 2001;  44 771-775
  PubMedGoogle Scholar
• 39 Peng H J, Turner M W, Strobel S. The kinetics of oral hyposensitization to a protein antigen are determined by immune status and the timing, dose and frequency of antigen administration.  Immunology. 1989;  44 425-430
  PubMedGoogle Scholar
• 40 Gutgemann I, Fahrer A M, Altman J D. et al . Induction of rapid T cell activation and tolerance by systemic presentation of an orally administered antigen.  Immunity. 1998;  44 667-673
  PubMedGoogle Scholar
• 41 Smith K M, Davidson J M, Garside P. T-cell activation occurs simultaneously in local and peripheral lymphoid tissue following oral administration of a range of doses of immunogenic or tolerogenic antigen although tolerized T cells display a defect in cell division.  Immunology. 2002;  44 144-158
  PubMedGoogle Scholar
• 42 Watanabe T, Katsukura H, Shirai Y. et al . A liver tolerates a portal antigen by generating CD11c+ cells, which select Fas ligand+ Th2 cells via apoptosis.  Hepatology. 2003;  44 403-412
  PubMedGoogle Scholar
• 43 Watanabe T, Yoshida M, Shirai Y. et al . Administration of an antigen at a high dose generates regulatory CD4 + T cells expressing CD95 ligand and secreting IL-4 in the liver.  J Immunol. 2002;  44 2188-2199
  PubMedGoogle Scholar
• 44 Regnault A, Lankar D, Lacabanne V. et al . Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization.  J Exp Med. 1999;  44 371-380
  PubMedGoogle Scholar
• 45 Limmer A, Ohl J, Wingender G. et al . Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance.  Eur J Immunol. 2005;  44 2970-2981
  PubMedGoogle Scholar
• 46 Campos R A, Szczepanik M, Itakura A. et al . Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity.  J Exp Med. 2003;  44 1785-1796
  PubMedGoogle Scholar

MD Percy A. Knolle

Institute for Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-University Bonn, University Hospital

Sigmund-Freud-Str. 25

53105 Bonn

Phone: ++ 49/2 28/2 87-10 50

Email: Percy.Knolle@ukb.uni-bonn.de