title: Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.
abstract: BACKGROUND
  Pertussis toxin (PTX), an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE) in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.
  
  
  RESULTS
  We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH) responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180), encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55) or ovalbumin (OVA). PTX injection of mice immunized to IRBP peptide161-180 led to (i) the development of EAU as shown by histopathology of the retina, (ii) pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii) symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.
  
  
  CONCLUSIONS
  The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards the tissue site of the autoantigen.
authors.affiliation: Department of Immunology, Connecticut Lions Vascular Vision Center, The University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: Rajwahrdhan
authors.initials: R
authors.lastname: Yadav
authors.forename: Sourojit
authors.initials: S
authors.lastname: Bhowmick
authors.forename: Philip
authors.initials: P
authors.lastname: Gorecki
authors.forename: James
authors.initials: J
authors.lastname: O'Rourke
authors.forename: Robert E
authors.initials: RE
authors.lastname: Cone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000737:chemistry; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D037342:Pertussis Toxin / Q000494:pharmacology*; D012177:Retinol-Binding Proteins / Q000737:chemistry; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D001324:Autoantigens; D016207:Cytokines; D005136:Eye Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin; D010446:Peptide Fragments; D037342:Pertussis Toxin; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C571326:MOG protein, human; C571327:Mog protein, mouse