title: The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment.
abstract: OBJECTIVE
  Experimental autoimmune uveoretinitis (EAU) in mice is an important model for elucidating basic mechanisms in autoimmune eye disease. The need for pertussis toxin (PTX) as an additional adjuvant to elicit EAU has limited the usefulness of this model in some types of studies by introducing a pleiotropic factor with confounding effects on the immune response.
  
  
  METHODS
  In the present study the authors examined the ability of B10.RIII mice, the most susceptible strain known so far, to develop EAU in response to the retinal antigen, interphotoreceptor retinoid-binding protein (IRBP), and to a major uveitogenic epitope of IRBP, peptide (p)161-180, in the absence of PTX treatment.
  
  
  RESULTS
  The data indicate that high disease scores in response to IRBP and p161-180 were found in B10.RIII mice, without the need for PTX as part of the immunization protocol. Unlike the B10.A strain in which appreciable disease did not develop without PTX, B10.RIII mice mounted a high IFN-gamma response to IRBP in the absence of PTX treatment. Interestingly, and unlike the effect with IRBP, in vitro recall response to p161-180 was low in IFN-gamma, despite good EAU scores.
  
  
  CONCLUSIONS
  The data indicate that an important mechanism through which PTX facilitates induction of cell-mediated autoimmunity is by promoting a Th1 polarization of the immune response. The propensity of B10.RIII mice to mount a more polarized Th1 response to IRBP than other strains may contribute to their ability to develop EAU without pertussis adjuvant. Nevertheless, the induction of EAU by p161-180 in the context of a relatively limited IFN-gamma production indicates that non-Th1- and Th-related mechanisms are likely to act in concert to determine the outcome of disease.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Silver
authors.forename: C C
authors.initials: CC
authors.lastname: Chan
authors.forename: B
authors.initials: B
authors.lastname: Wiggert
authors.forename: R R
authors.initials: RR
authors.lastname: Caspi
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin; D015203:Reproducibility of Results; D012173:Retinitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*; D014605:Uveitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005136:Eye Proteins; D010446:Peptide Fragments; D037342:Pertussis Toxin; D012177:Retinol-Binding Proteins; D010566:Virulence Factors, Bordetella; D000099214:Retinol-Binding Proteins, Interstitial