Abstract
Autoimmune disorders are diseases in which a vigorous immune reaction against certain self-antigens is induced, leading to pathological damage either in one organ or generalized in various tissues in the body. Generally, the immune system maintains a status of unresponsivenes towards self-antigens, while being able to mount an immune response against pathogen-derived antigens. Tolerance, at least on the level of T cells, is established and maintained by elimination of self-reactive cells in the thymus or, alternatively, when antigens are immunologically ignored because they are expressed at immunologically sequestered sites1-3 or when antigens do not reach a certain concentration level in lymphoid organs45. Thus, the decision whether an autoimmune reaction is initiated is probably made when a previously ignored antigen is presented in sufficient amounts and over a certain time in secondary lymphoid tissues. It is likely that antigen presentation by professional antigen presenting cells, i.e. dendritic cells and macrophages, in lymphoid tissues is the key step in the initiation of an anti-self response and to break the status of ignorance. Accordingly, the central questions for the initiation of T cell-mediated autoimmune diseases are ‘Which are the antigens that induce the primary immune response against the target organ?’ and ‘Which mechanisms lead to release of tissue antigen and subsequent presentation of these antigens in secondary lymphoid organs?’.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Barker CF, Billingham RE. Immunologically privileged sites. Adv. Immunol. 1972.25:1.
Ohashi PS, Oehen S, Buerki K et al. Ablation of ‘tolerance’ and induction of diabetes by virus infection in viral antigen transgenic mice. Cell.1991;65:305–317.
Oldstone MB, Nerenberg M, Southern P, Price J, Lewicki H. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell. 1991;65:319–331.
Ferber I, Schonrich G, Schenkel J, Mellor AL, Arnold B, Hammerling GJ. Levels of peripheral T cell tolerance induced by different doses of tolerogen. Science. 1994;263:674–676.
Kurts C, Heath WR, Kosaka H, Miller JF, Carbone FR. The peripheral deletion of autoreactive CD8+ T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1). J Exp Med. 1998;188:415–420.
Oldstone MB. Molecular mimicry and autoimmune disease. Cell 1987;50:819–820.
Oldstone MB. Molecular mimicry as a mechanism for the cause and a probe uncovering etiologic agent(s) of autoimmune disease. Curr Top Microbiol Immunol. 1989;145:127–135.
Tough DF, Borrow P, Sprent J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science. 1996;272:1947–1950.
Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 1998;4:781–785.
Zinkernagel RM. Immunology taught by viruses. Science. 1996;271:173–178.
Cole GA, Nathanson N, Prendergast RA. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 1972;238:335–337.
Zinkernagel RM, Haenseler E, Leist T, Cerny A, Hengartner H, Althage A. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class 1-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? J Exp Med. 1986;164:1075–1092.
Odermatt B, Eppler M, Leist TP, Hengartner H, Zinkernagel RM. Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure. Proc Natl Acad Sci USA. 1991;88:8252–8256.
Kagi D, Seiler P, Pavlovic J et al. The roles of perforin-and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. Eur J Immunol. 1995;25:3256–3262.
Miller SD, Vanderlugt CL, Begolka WS et al. Persistent infection with Theiler’s virus leads to CNS autoimmunity via epitope spreading. Nat Med. 1997;3:1133–1136.
Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296.
Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–252.
Moll H. Epidermal Langerhans cells are critical for immunoregulation of cutaneous leishmaniasis. Immunol Today 1993;14:383–387.
Spira AI, Marx PA, Patterson BK et al. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med. 1996;183:215–225.
Masurier C, Salomon B, Guettari N et al. Dendritic cells route human immunodeficiency virus to lymph nodes after vaginal or intravenous administration to mice. J Virol. 1998;72:7822–7829.
Kimber I, Cumberbatch M. Stimulation of Langerhans cell migration by tumor necrosis factor alpha (TNF-alpha).J Invest Dermatol. 1992;99:48–50S.
Roake JA, Rao AS, Morris PJ, Larsen CP, Hankins DF, Austyn JM. Systemic lipopolysaccharide recruits dendritic cell progenitors to nonlymphoid tissues. Transplantation, 1995;59:1319–1324.
DeSmedt T, Pajak B, Muraille E et al. Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J Exp Med. 1996;184:1413–1424.
Ehl S, Hombach J, Aichele P et al. Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology. J Exp Med. 1998;187:763–774.
Ludewig B, Odermatt B, Landmann S, Hengartner H, Zinkernagel RM. Dendritic cells induce autoimmune diabetes and maintain disease via de novoformation of local lymphoid tissue. J Exp Med. 1998;188:1493–1501.
Ludewig B, Ehl S, Karrer U, Odermatt B, Hengartner H, Zinkernagel RM. Dendritic cells efficiently induce protective antiviral immunity. J Virol. 1998;72:3812–3818.
Carbone FR, Kurts C, Bennett SR, Miller JF, Heath WR. Cross-presentation: a general mechanism for CTL immunity and tolerance. Immunol Today. 1998;19:368–3673.
Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature. 1997;388:782–787.
Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392:86–89.
Ohashi PS, Oehen S, Aichele P et al. Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-α. J. Immunol. 1993;150:5185–5194.
Higuchi Y, Herrera P, Muniesa P et al. Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med. 1992;176:1719–1731.
Von Herrath MG, Allison J, Miller JF, Oldstone MB. Focal expression of interleukin-2 does not break unresponsiveness to’ self (viral) antigen expressed in beta cells but enhances development of autoimmune disease (diabetes) after initiation of an anti-self immune response. J Clin Invest. 1995;95:477–485.
Harlan DM, Hengartner H, Huang ML et alMice expressing both B7–1 and viral glycoprotein on pancreatic beta cells along with glycoprotein-specific transgenic T cells develop diabetes due to a breakdown of T-lymphocyte unresponsiveness. Proc Natl Acad Sci USA. 1994;91:3137–3141.
Melief MJ, Hoijer MA, Van Paassen HC, Hazenberg MP. Presence of bacterial flora-derived antigen in synovial tissue macrophages and dendritic cells. Br J Rheumatol. 1995;34:1112–1116.
Kabel PJ, Voorbij HA, de Haan-Meulman M, Pals ST, Drexhage HA. High endothelial venules present in lymphoid cell accumulations in thyroids affected by autoimmune disease: a study in men and BB rats of functional activity and development. J Clin Endocrinol Metab. 1989;68:744–751.
Jansen A, Voorbij HA, Jeucken PH, Bruining GJ, Hooijkaas H, Drexhage HA. An immunohisto-chemical study on organized lymphoid cell infiltrates in fetal and neonatal pancreases. A comparison with similar infiltrates found in the pancreas of a diabetic infant. Autoimmunity. 1993;15:31–38.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Proc Natl Acad Sci USA. 1992;89:10036–10040.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. J Immunol. 1993;150:4136–4150.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Ludewig, B., Aichele, P., Zinkernagel, R.M., Hengartner, H. (2000). Mechanisms of virus-induced autoimmune disease. In: Manns, M.P., Paumgartner, G., Leuschner, U. (eds) Immunology and Liver. Falk Symposium, vol 114. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4000-3_5
Download citation
DOI: https://doi.org/10.1007/978-94-011-4000-3_5
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-5768-4
Online ISBN: 978-94-011-4000-3
eBook Packages: Springer Book Archive