Kinetics of IL-17- and interferon-γ-producing PLPp-specific CD4 T cells in EAE induced by coinjection of PLPp/IFA with pertussis toxin in SJL mice

doi:10.1016/j.neulet.2010.04.018

Neuroscience Letters

Volume 476, Issue 3, 7 June 2010, Pages 150-155

https://doi.org/10.1016/j.neulet.2010.04.018 Get rights and content

Abstract

Systemic administration of Pertussis toxin (PTX) abrogates T cell tolerance mediated by injection of neuroantigens in incomplete Freund's adjuvant (IFA) and causes experimental autoimmune encephalomyelitis (EAE). PTX concomitantly induces high frequencies of neuroantigen-specific IFN-γ- and IL-17-producing T cells. Both IL-17 and IFN-γ have been implicated as a key effector cytokines in the pathogenesis of EAE, possibly with different functions. We therefore investigated potential differences in the temporal and spatial kinetics of the PTX-induced neuroantigen-specific IFN-γ- and IL-17-producing T cell effector populations. IFN-γ- and IL-17-producing PLPp-specific T cells initially arose in comparable frequencies in the local draining lymph nodes (drLN) after immunization as measured by cytokine ELISPOT. High frequencies of both IFN-γ- and IL-17-producing T cells were present in the immune periphery before onset of EAE. The highest frequencies of PTX-induced IFN-γ- and IL-17-producing PLPp-specific cells coincided in the inflamed CNS during acute EAE. During recovery, both IFN-γ- and IL-17-producing PLPp-specific T cells simultaneously disappeared from the CNS, whereas high frequencies of these cells remained present in the immune periphery. The functional affinity of both IFN-γ- and IL-17-producing T cells did not change during EAE. Therefore, autoimmune pathology in this model did not correlate with specific PTX effects either on Th1 or Th17 cells regarding their kinetics and CNS migration.

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Acknowledgements

We thank Prof. Dr. Klaus V. Toyka (Department of Neurology, University of Würzburg) for helpful comments and support throughout the study. We thank Mrs. Rocio Guardia for excellent technical assistance. This work was supported by grants NS42809 from the National Institutes of Health and RG 3322 from the National Multiple Sclerosis Society (T.G.F.). In addition, it was supported by a travel scholarship of the European Neurological Society to H.H.H., a non-restricted research grant of Biogen Idec

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Kinetics of IL-17- and interferon-γ-producing PLPp-specific CD4 T cells in EAE induced by coinjection of PLPp/IFA with pertussis toxin in SJL mice

Abstract

Section snippets

Acknowledgements

J. Biol. Chem.

Am. J. Pathol.

J. Neuroimmunol.

Am. J. Pathol.

Cell. Immunol.

Cytokine

Semin. Immunol.

Neurosci. Lett.

J. Neuroimmunol.

Am. J. Pathol.

IL-17: prototype member of an emerging cytokine family

J. Leukoc. Biol.

Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12

J. Clin. Invest.

Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma

J. Immunol.

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Nature

Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE)

J. Immunol.

Increased expression of interleukin 17 in inflammatory bowel disease

Gut

IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice

J. Clin. Invest.