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Modelling Gene-Environment Interactions in Th1- and Th2-Dominated Diseases of Laboratory Animals

  • Conference paper
Animal Models of T Cell-Mediated Skin Diseases

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 50))

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3.6 Conclusions

In conclusion, the “old friends hypothesis” seeks to explain the increasing prevalence of many chronic inflammatory disorders as a failure of immunoregulation secondary to decreased exposure to certain microorganisms that have been present throughout our evolutionary history. It is argued that these organisms are effectively part of our physiology, and are recognised as harmless by the innate immune system, which then activates immunoregulatory circuits, including Treg and regulatory APCs. The “old friends” consequently act as adjuvants for other antigens such as self, allergens, and gut contents, and so limit chronic inflammatory immunoregulatory disorders. These mechanisms can be revealed by altering the microbial exposure, or by studying the presence of polymorphisms of the innate immune system, since these two factors provide a series of classical gene-environment interactions. An important consequence of this understanding is the fact that the enormous variability of animal models of inflammatory disorders in different laboratories can now be exploited to investigate these gene-environment interactions. Experiments based on these differences, perhaps involving collaborations between laboratories, or the use of gnotobiotic mice reconstituted with one or a few microbial species, can be applied to those animal models where variable microbial exposure is already known to exert a profound influence.

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References

  • Alm JS, Sanjeevi CB, Miller EN et al (2002) Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471. Genes Immun 3:71–77

    Article  PubMed  CAS  Google Scholar 

  • Arkwright PD, David TJ (2001) Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. J Allergy Clin Immunol 107:531–534

    Article  PubMed  CAS  Google Scholar 

  • Asadullah K, Sterry W, Volk HD (2003) Interleukin-10 therapy; review of a new approach. Pharmacol Rev 55:241–269

    Article  PubMed  CAS  Google Scholar 

  • Asea A, Rehli M, Kabingu E et al (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034

    Article  PubMed  CAS  Google Scholar 

  • Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347:911–920

    Article  PubMed  Google Scholar 

  • Baker BS, Ovigne JM, Powles AV et al (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148:670–679

    Article  PubMed  CAS  Google Scholar 

  • Baldini M, Lohman IC, Halonen M et al (1999) A Polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol 20:976–983

    PubMed  CAS  Google Scholar 

  • Belkaid Y, Piccirillo CA, Mendez S et al (2002) CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420:502–507

    Article  PubMed  CAS  Google Scholar 

  • Braun-Fahrlander C, Riedler J, Herz U et al (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347:869–877

    Article  PubMed  Google Scholar 

  • Breban MA, Moreau MC, Fournier C et al (1993) Influence of the bacterial flora on collagen-induced arthritis in susceptible and resistant strains of rats. Clin Exp Rheumatol 11:61–64

    PubMed  CAS  Google Scholar 

  • Brunkow ME, Jeffery EW, Hjerrild KA et al (2001) Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 27:68–73

    Article  PubMed  CAS  Google Scholar 

  • Bulut Y, Faure E, Thomas L et al (2002) Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 168:1435–1440

    PubMed  CAS  Google Scholar 

  • Camporota L, Corkhill A, Long H et al (2003) The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma. Eur Respir J 21:287–293

    Article  PubMed  CAS  Google Scholar 

  • Caramalho I, Lopes-Carvalho T, Ostler D et al (2003) Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 197:403–411

    Article  PubMed  CAS  Google Scholar 

  • Contractor NV, Bassiri H, Reya T et al (1998) Lymphoid hyperplasia, autoimmunity, and compromised intestinal intraepithelial lymphocyte development in colitis-free gnotobiotic IL-2-deficient mice. J Immunol 160: 385–394

    PubMed  CAS  Google Scholar 

  • Curry JL, Qin JZ, Bonish B et al (2003) Innate immune-related receptors in normal and psoriatic skin. Arch Pathol Lab Med 127:178–186

    PubMed  CAS  Google Scholar 

  • Douek IF, Leech NJ, Gillmor HA et al (1999) Children with type-1 diabetes and their unaffected siblings have fewer symptoms of asthma. Lancet 353:1850

    Article  PubMed  CAS  Google Scholar 

  • Dutronc Y, Porcelli SA (2002) The CD1 family and T cell recognition of lipid antigens. Tissue Antigens 60:337–353

    Article  PubMed  CAS  Google Scholar 

  • Edinger M, Hoffmann P, Ermann J et al (2003) CD4+CD25+ regulatory T cells preserve graft-versus-tumour activity while inhibiting graft-versus-host disease after bone-marrow transplantation. Nat Med 9:1144–1150

    Article  PubMed  CAS  Google Scholar 

  • Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4(+)CD25(+) regulatory T cells. Nat Immunol 4:330–336

    Article  PubMed  CAS  Google Scholar 

  • Ghoreschi K, Thomas P, Breit S et al (2003) Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 9:40–46

    Article  PubMed  CAS  Google Scholar 

  • Groux H, O’Garra A, Bigler M et al (1997) A CD4+ subset inhibits antigen-specific T cell responses and prevents colitis. Nature 389:737–742

    Article  PubMed  CAS  Google Scholar 

  • Hanngren A, Odham G, Eklund A et al (1987) Tuberculostearic acid in lymph nodes from patients with sarcoidosis. Sarcoidosis 4:101–104

    PubMed  CAS  Google Scholar 

  • Hansen G, Berry G, DeKruyff RH et al (1999) Allergen-specific Thl cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103:175–183

    Article  PubMed  CAS  Google Scholar 

  • Heldwein KA, Fenton MJ (2002) The role of Toll-like receptors in immunity against mycobacterial infection. Microbes Infect 4:937–944

    Article  PubMed  CAS  Google Scholar 

  • Hensen P, Asadullah K, Windemuth C et al (2003) Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis. Br J Dermatol 149:381–385

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Pando R, Aguilar D, Garcia Hernandez ML et al (2003) Pulmonary tuberculosis in Balb/c mice with non-functional IL-4 genes; changes in the inflammatory effects of TNF-α in the regulation of fibrosis. Eur J Immunol 34:174–183

    Article  CAS  Google Scholar 

  • Hikita I, Yoshioka T, Mizoguchi T et al (2002) Characterization of dermatitis arising spontaneously in DS-Nh mice maintained under conventional conditions: another possible model for atopic dermatitis. J Dermatol Sci 30:142–153

    Article  PubMed  CAS  Google Scholar 

  • Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061

    Article  PubMed  CAS  Google Scholar 

  • Jahnsen FL, Moloney ED, Hogan T et al (2001) Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge. Thorax 56:823–826

    Article  PubMed  CAS  Google Scholar 

  • Jones CA, Holloway JA, Popplewell EJ et al (2002) Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both. J Allergy Clin Immunol 109:858–866

    Article  PubMed  CAS  Google Scholar 

  • Kabesch M, Peters W, Carr D et al (2003) Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. J Allergy Clin Immunol 111:813–817

    Article  PubMed  CAS  Google Scholar 

  • Kalliomaki M, Isolauri E (2003) Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol 3:15–20

    Article  PubMed  CAS  Google Scholar 

  • Kalliomaki M, Salminen S, Arvilommi H et al (2001) Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial Lancet 357:1076–1079

    Article  PubMed  CAS  Google Scholar 

  • Karhukorpi J, Ikaheimo I, Karvonen J et al (2002) Promoter region polymorphism of the CD14 gene (C-159T) is not associated with psoriasis vulgaris. Eur J Immunogenet 29:57–60

    Article  PubMed  CAS  Google Scholar 

  • Kingo K, Koks S, Silm H et al (2003) IL-10 promoter polymorphisms influence disease severity and course in psoriasis. Genes Immun 4:455–457

    Article  PubMed  CAS  Google Scholar 

  • Kohashi O, Kohashi Y, Takahashi T et al (1985) Reverse effect of gram-positive bacteria vs. gram-negative bacteria on adjuvant-induced arthritis in germfree rats. Microbiol Immunol 29:487–497

    PubMed  CAS  Google Scholar 

  • Kojima Y, Kinouchi Y, Takahashi S et al (2001) Inflammatory bowel disease is associated with a novel promoter polymorphism of natural resistance-associated macrophage protein 1 (NRAMP1) gene. Tissue Antigens 58: 379–384.

    Article  PubMed  CAS  Google Scholar 

  • Kotze MJ, de Villiers JN, Rooney RN et al (2001) Analysis of the NRAMP1 gene implicated in iron transport: association with multiple sclerosis and age effects. Blood Cells Mol Dis 27:44–53

    Article  PubMed  CAS  Google Scholar 

  • Krug N, Madden J, Redington AE et al (1996) T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 14:319–326

    PubMed  CAS  Google Scholar 

  • Kukreja A, Maclaren NK (2002) NKT cells and type-1 diabetes and the “hygiene hypothesis” to explain the rising incidence rates. Diabetes Technol Ther 4:323–333

    Article  PubMed  CAS  Google Scholar 

  • Lammas DA, Casanova JL, Kumararatne DS (2000) Clinical consequences of defects in the IL-12-dependent interferon-gamma (IFN-gamma) pathway. Clin Exp Immunol 121:417–425

    Article  PubMed  CAS  Google Scholar 

  • Lauener RP, Birchler T, Adamski J et al (2002) Expression of CD14 and Toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet 360: 465–466

    Article  PubMed  CAS  Google Scholar 

  • Lim S, Crawley E, Woo P et al (1998) Haplotype associated with low interleukin-10 production in patients with severe asthma. Lancet 352:113

    Article  PubMed  CAS  Google Scholar 

  • Lindberg E, Lindquist B, Holmquist L et al (2000) Inflammatory bowel disease in children and adolescents in Sweden, 1984–1995. J Pediatr Gastroenterol Nutr 30:259–264

    Article  PubMed  CAS  Google Scholar 

  • Matricardi PM, Rosmini F, Riondino S et al (2000) Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma; epidemiological study. Brit Med J 320:412–417

    Article  PubMed  CAS  Google Scholar 

  • McIntire JJ, Umetsu SE, Akbari O et al (2001) Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nat Immunol 2:1109–1116

    Article  PubMed  CAS  Google Scholar 

  • Moudgil KD, Kim E, Yun OJ et al (2001) Environmental modulation of autoimmune arthritis involves the spontaneous microbial induction of T cell responses to regulatory determinants within heat shock protein 65. J Immunol 166:4237–4243

    PubMed  CAS  Google Scholar 

  • Najarian DJ, Gottlieb AB (2003) Connections between psoriasis and Crohn’s disease. J Am Acad Dermatol 48:805–821; quiz 822–824

    Article  PubMed  Google Scholar 

  • Nickoloff BJ (1999) Skin innate immune system in psoriasis: friend or foe? J Clin Invest 104:1161–1164

    Article  PubMed  CAS  Google Scholar 

  • O’Neill LA (2002) Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal? Trends Immunol 23:296–300

    Article  PubMed  CAS  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  PubMed  CAS  Google Scholar 

  • Oppmann B, Lesley R, Blom B et al (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725

    Article  PubMed  CAS  Google Scholar 

  • Pasare C, Medzhitov R (2003) Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299:1033–1036

    Article  PubMed  CAS  Google Scholar 

  • Penhale WJ, Young PR (1988) The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroiditis. Clin Exp Immunol 72:288–292

    PubMed  CAS  Google Scholar 

  • Raby BA, Klimecki WT, Laprise C et al (2002) Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Am J Respir Crit Care Med 166:1449–1456

    Article  PubMed  Google Scholar 

  • Rachmilewitz D, Karmeli F, Takabayashi K et al (2002) Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology 122:1428–1441

    Article  PubMed  CAS  Google Scholar 

  • Rahman P, Bartlett S, Siannis F et al (2003) CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis. Am J Hum Genet 73:677–681

    Article  PubMed  CAS  Google Scholar 

  • Rath HC (2002) Role of commensal bacteria in chronic experimental colitis: lessons from the HLA-B27 transgenic rat. Pathobiology 70:131–138

    Article  PubMed  CAS  Google Scholar 

  • Re F, Strominger JL (2001) Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J Biol Chem 276:37692–37699

    Article  PubMed  CAS  Google Scholar 

  • Rehakova Z, Capkova J, Stepankova R et al (2000) Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease. Hum Immunol 61:555–558

    Article  PubMed  CAS  Google Scholar 

  • Riedler J, Braun-Fahrlander C, Eder W et al (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129–1133

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez MR, Gonzalez-Escribano MF, Aguilar F et al (2002) Association of NRAMP1 promoter gene polymorphism with the susceptibility and radiological severity of rheumatoid arthritis. Tissue Antigens 59:311–315

    Article  PubMed  CAS  Google Scholar 

  • Rook GA, Brunet LR (2002) Give us this day our daily germs. Biologist (London) 49:145–149

    PubMed  Google Scholar 

  • Rook GA, Martinelli R, Brunet LR (2003) Innate immune responses to mycobacteria and the downregulation of atopic responses. Curr Opin Allergy Clin Immunol 3:337–342

    Article  PubMed  CAS  Google Scholar 

  • Rook GAW (2000) Clean living increases more than atopic disease. Immunology Today 21:249

    Article  PubMed  CAS  Google Scholar 

  • Rook GAW, Stanford JL (1998) Give us this day our daily germs. Immunol Today 19:113–116

    Article  PubMed  CAS  Google Scholar 

  • Satoguina J, Mempel M, Larbi J et al (2002) Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes Infect 4:1291–1300

    Article  PubMed  CAS  Google Scholar 

  • Sawczenko A, Sandhu BK, Logan RF et al (2001) Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet 357:1093–1094

    Article  PubMed  CAS  Google Scholar 

  • Schultz M, Veltkamp C, Dieleman LA et al (2002) Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflammatory Bowel Diseases 8:71–80

    Article  PubMed  Google Scholar 

  • Seddon B, Mason D (1999) Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC-cells and CD4(+)CD8(-) thymocytes. J Exp Med 189: 279–288

    Article  PubMed  CAS  Google Scholar 

  • Sengler C, Haider A, Sommerfeld C et al (2003) Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort. Clin Exp Allergy 33:166–169

    Article  PubMed  CAS  Google Scholar 

  • Sepp E, Julge K, Vasar M et al (1997) Intestinal microflora of Estonian and Swedish infants. Acta Paediatr 86:956–961

    Article  PubMed  CAS  Google Scholar 

  • Smit JJ, Van Loveren H, Hoekstra MO et al (2003) Influence of the macrophage bacterial resistance gene Nrampl (Slc11a1) on the induction of allergic asthma in the mouse. FASEB J 17:958–960

    PubMed  CAS  Google Scholar 

  • Stanford JL, Nye PM, Rook GA et al (1981) A preliminary investigation of the responsiveness or otherwise of patients and staff of a leprosy hospital to groups of shared or species antigens of mycobacteria. Lepr Rev 52: 321–327

    PubMed  CAS  Google Scholar 

  • Steel C, Nutman TB (2003) CTLA-4 in filarial infections: implications for a role in diminished T cell reactivity. J Immunol 170:1930–1938

    PubMed  CAS  Google Scholar 

  • Stene LC, Nafstad P (2001) Relation between occurrence of type 1 diabetes and asthma. Lancet 357:607

    Article  PubMed  CAS  Google Scholar 

  • Strachan DP, Taylor EM, Carpenter RG (1996) Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child 74:422–426

    Article  PubMed  CAS  Google Scholar 

  • Sudo N, Sawamura S, Tanaka K et al (1997) The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol 159:1739–1754

    PubMed  CAS  Google Scholar 

  • Sudo N, Yu XN, Aiba Y et al (2002) An oral introduction of intestinal bacteria prevents the development of a long-term Th2-skewed immunological memory induced by neonatal antibiotic treatment in mice. Clin Exp Allergy 32:1112–1116

    Article  PubMed  CAS  Google Scholar 

  • Taurog JD, Richardson JA, Croft JT et al (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180:2359–2364

    Article  PubMed  CAS  Google Scholar 

  • Thompson SJ, Elson CJ (1993) Susceptibility to pristane-induced arthritis is altered with changes in bowel flora. Immunol Lett 36:227–231

    Article  PubMed  CAS  Google Scholar 

  • Tomita K, Lim S, Hanazawa T et al (2002) Attenuated production of intracellular IL-10 and IL-12 in monocytes from patients with severe asthma. Clin Immunol 102:258–266

    Article  PubMed  CAS  Google Scholar 

  • Tremlett HL, Evans J, Wiles CM et al (2002) Asthma and multiple sclerosis: an inverse association in a case-control general practice population. Qjm 95:753–756

    Article  PubMed  CAS  Google Scholar 

  • Umetsu DT, McIntire JJ, Akbari O et al (2002) Asthma: an epidemic of dysregulated immunity. Nat Immunol 3:715–720

    Article  PubMed  CAS  Google Scholar 

  • van de Langerijt AG, van Lent PL, Hermus AR et al (1994) Susceptibility to adjuvant arthritis: relative importance of adrenal activity and bacterial flora. Clin Exp Immunol 97:33–38

    PubMed  Google Scholar 

  • van den Biggelaar AH, van Ree R, Rodrigues LC et al (2000) Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356:1723–1727

    Article  PubMed  Google Scholar 

  • van den Broek MF, van Bruggen MC, Koopman JP et al (1992) Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats. Clin Exp Immunol 88:313–317

    PubMed  Google Scholar 

  • Van der Kleij D, Latz E, Brouwers JF et al (2002) A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J Biol Chem 277:48122–48129

    Article  PubMed  Google Scholar 

  • Van der Kleij D, Van Remoortere A, Schuitemaker JH et al (2002) Triggering of innate immune responses by schistosome egg glycolipids and their carbohydrate epitope GalNAc beta 1–4(Fuc alpha l–2Fuc alpha 1–3) GlcNAc. J Infect Dis 185:531–539

    Article  PubMed  Google Scholar 

  • Van Eden W, Koets A, van Kooten P et al (2003) Immunopotentiating heat shock proteins: negotiators between innate danger and control of autoimmunity. Vaccine 21:897–901

    Article  PubMed  Google Scholar 

  • Verdu EF, Bercik P, Cukrowska B et al (2000) Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice. Clinical and Experimental Immunology 120:46–50

    Article  PubMed  CAS  Google Scholar 

  • Vincent MS, Leslie DS, Gumperz JE et al (2002) CDl-dependent dendritic cell instruction. Nat Immunol 3:1163–1168

    Article  PubMed  CAS  Google Scholar 

  • Watanabe A, Takeuchi M, Nagata M et al (2003) Spontaneous development of dermatitis in DS-Nh mice under specific pathogen-free conditions. Exp Anim 52:77–80

    Article  PubMed  CAS  Google Scholar 

  • Wildin RS, Ramsdell F, Peake J et al (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27:18–20

    Article  PubMed  CAS  Google Scholar 

  • Yazdanbakhsh M, Kremsner PG, van Ree R (2002) Allergy, Parasites, and the Hygiene Hypothesis. Science 296:490–494

    Article  PubMed  CAS  Google Scholar 

  • Zuany-Amorim C, Manlius C, Trifilieff A et al (2002) Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation. J Immunol 169:1492–1499

    PubMed  CAS  Google Scholar 

  • Zuany-Amorim C, Sawicka E, Manlius C et al (2002) Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8:625–629

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, 46 Cleveland Street, London, W1P 6DB, UK

    G. A. W. Rook

  2. SR Pharma, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, 46 Cleveland Street, London, W1P 6DB, UK

    R. Martinelli & L. Rosa Brunet

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  1. G. A. W. Rook
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  2. R. Martinelli
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  1. Corporate Research Business Area Dermatology, Schering AG, Müllerstr. 178, 13342, Berlin, Germany

    T. Zollner  & K. Asadullah  & 

  2. Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps-University, Baldinger Straße, 35034, Marburg, Germany

    H. Renz

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Rook, G.A.W., Martinelli, R., Rosa Brunet, L. (2005). Modelling Gene-Environment Interactions in Th1- and Th2-Dominated Diseases of Laboratory Animals. In: Zollner, T., Renz, H., Asadullah, K. (eds) Animal Models of T Cell-Mediated Skin Diseases. Ernst Schering Research Foundation Workshop, vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26811-1_3

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