Dissociating the enhancing and inhibitory effects of pertussis toxin on autoimmune disease.
Pertussis toxin (PT) has both enhancing and inhibitory effects on experimental autoimmune disease, depending on its time of administration relative to immunization. The inhibitory effect is due to blocking of G(i)-coupled receptors by the enzymatic A subunit. In this study, we attribute the enhancing effect of PT to the cell-binding B subunit (PT-B). C57BL/6 mice, a strain that requires PT to develop experimental uveitis, were immunized with a retinal Ag and were injected with whole PT, PT-B, or vehicle. Disease and associated immunological responses were evaluated. The results showed that PT-B, determined to be free of biologically significant contamination with whole PT or with endotoxin, was able to mimic all the effects of PT with respect to disease induction, enhancement of delayed-type hypersensitivity, enhancement of lymphocyte proliferation, induction of an innate IL-12 response, and promotion of an adaptive IFN-gamma response to the uveitogenic Ag. Our results suggest that PT-B is largely responsible for the disease-enhancing properties of PT.
Su
Shao Bo
SB
Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Silver
Phyllis B
PB
Wang
Peng
P
Chan
Chi-Chao
CC
Caspi
Rachel R
RR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004340:Drug Contamination; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry / Q000276:immunology; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D021122:Protein Subunits / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D021122:Protein Subunits; D018664:Interleukin-12; D037342:Pertussis Toxin