Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund's adjuvant: induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells.
Pertussis toxin (PT) has been widely used to facilitate the induction of experimental autoimmune encephalomyelitis (EAE) in rodents. It has been suggested that this microbial product promotes EAE by opening up the blood-brain barrier and thereby facilitates the migration of pathogenic T cells to the CNS. However, PT has other biological effects that could contribute to its activity in EAE, such as enhancing the cytokine production by T cells and induction of lymphocytosis. In this work, we investigated the effects of PT on the pathogenicity, cytokine differentiation, and clonal sizes of neuroantigen-reactive T cells in EAE in mice. Our results show that PT prevented the protection from EAE conferred by injection of PLPp139-151 in IFA and induced high frequencies of peptide-specific Th1 cells and disease. Interestingly, the mice developed EAE despite the simultaneous vigorous clonal expansion of PLPp139-151-specific Th2 cells. The data indicate that the Th2 cells in this model neither were protective against EAE nor promoted the disease. Furthermore, the results suggested that the effects of the toxin on neuroantigen-reactive T cells were promoted by the PT-induced activation of APCs in lymphoid tissues and the CNS. Together, the results suggest that microbial products, such as PT, could contribute to the initiation of autoimmune disease by modulating the interaction between the innate and adaptive immune system in the response to self Ags.
Hofstetter
Harald H
HH
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4943, USA.
Shive
Carey L
CL
Forsthuber
Thomas G
TG
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D007108:Immune Tolerance; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008055:Lipids; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D037342:Pertussis Toxin; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D018984:Epitopes, T-Lymphocyte; D008055:Lipids; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; C114843:incomplete Freund's adjuvant; C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant; D037342:Pertussis Toxin