Altered neuroantigen-specific cytokine secretion in a Th2 environment reduces experimental autoimmune encephalomyelitis

Kirwin, Stefanie J.; Dowdell, Kenichi C.; Hindinger, Claudia; Feng, Ni; Bergmann, Cornelia C.; Hinton, David R.; Stohlman, Stephen A.

doi:10.1016/j.jneuroim.2006.05.015

« Previous Next »Journal of Neuroimmunology
Volume 178, Issue 1 , Pages 30-39, September 2006

Altered neuroantigen-specific cytokine secretion in a Th2 environment reduces experimental autoimmune encephalomyelitis

Stefanie J. Kirwin
- Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
Kenichi C. Dowdell
- Department of Neurology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Present address: NIAID, Laboratory of Clinical Infectious Diseases, Bethesda, MD 20892, USA.
Claudia Hindinger
- Department of Neurology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Present address: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.
Ni Feng
- Department of Neurology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
Cornelia C. Bergmann
- Department of Neurology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Department of Pathology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Present address: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.
David R. Hinton
- Department of Pathology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
Stephen A. Stohlman
- Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Department of Neurology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Department of Pathology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA
- Corresponding author. Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 1333 San Pablo Ave, Los Angeles, CA 90033, USA. Tel.: +1 216 445 9796; fax: +1 216 444 7927.

Received 29 March 2006; received in revised form 8 May 2006; accepted 18 May 2006. published online 03 July 2006.

Abstract

Activation of Th2 cells suppresses clinical experimental autoimmune encephalitis (EAE), demyelination and expression of genes associated with Th1-mediated inflammation. Despite both reduced central nervous system inflammation and IFN-γ induced MHC class II expression by microglia, the composition of CNS infiltrates in Th2-protected mice were similar to mice with EAE. Analysis of the CNS infiltrating cells by flow cytometry suggests that protection did not correlate with abrogation of CD4⁺ T cell recruitment, preferential recruitment of donor Th2 cells or an increased frequency of CD25⁺ CD4⁺ T cells. By contrast, protection correlated with an increased frequency of neuroantigen-specific Th2 cells infiltrating the CNS. These data suggest that a peripheral Th2 cytokine environment influences both potential antigen presenting cells as well as recruitment and/or retention of neuroAg-specific Th2 CD4⁺ T cells.

Abbreviations: EAE, experimental allergic encephalomyelitis, CNS, central nervous system, MS, multiple sclerosis, Ag, antigen, IFN, interferon, MBP, myelin basic protein, IL, interleukin, APC, antigen presenting cell, PLP, proteolipid protein, KLH, keyhole lympit hemocyanin, MHC, major histocompatibility complex