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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.
J Immunol. 2002 Jul 01; 169(1):117-25.JI

Abstract

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.

Authors+Show Affiliations

Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4943, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12077236

Citation

Hofstetter, Harald H., et al. "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." Journal of Immunology (Baltimore, Md. : 1950), vol. 169, no. 1, 2002, pp. 117-25.
Hofstetter HH, Shive CL, Forsthuber TG. 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. J Immunol. 2002;169(1):117-25.
Hofstetter, H. H., Shive, C. L., & Forsthuber, T. G. (2002). 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. Journal of Immunology (Baltimore, Md. : 1950), 169(1), 117-25.
Hofstetter HH, Shive CL, Forsthuber TG. 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. J Immunol. 2002 Jul 1;169(1):117-25. PubMed PMID: 12077236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hofstetter,Harald H, AU - Shive,Carey L, AU - Forsthuber,Thomas G, PY - 2002/6/22/pubmed PY - 2002/8/14/medline PY - 2002/6/22/entrez SP - 117 EP - 25 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 169 IS - 1 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/12077236/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_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=12077236 DB - PRIME DP - Unbound Medicine ER -