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International Immunology Advance Access originally published online on October 11, 2009
International Immunology 2009 21(12):1329-1340; doi:10.1093/intimm/dxp100
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Regulatory and pro-inflammatory phenotypes of myelin basic protein-autoreactive T cells in multiple sclerosis

Jian Hong1, Haiyan Li2, Meiyue Chen1, Ying C. Q. Zang1, Sheri M. Skinner1, James M. Killian1 and Jingwu Z. Zhang1,2

1 Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
2 Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China

Correspondence to: J. Hong; E-mail: jhong{at}bcm.edu

MBP-specific autoreactive T cells are considered pro-inflammatory T cells and thought to play an important role in the pathogenesis of multiple sclerosis (MS). Here, we report that MBP83–99-specific T cells generated from MS patients (n = 7) were comprised of pro-inflammatory and regulatory subsets of distinct phenotypes. The pro-inflammatory phenotype was characterized by high production of IFN-{gamma}, IL-6, IL-21 and IL-17 and low expression of FOXP3, whereas the regulatory subset expressed high levels of FOXP3 and exhibited potent regulatory functions. The regulatory subset of MBP-specific T cells appeared to expand from the CD4+CD25– T-cell pool. Their FOXP3 expression was stable, independent of the activation state and it correlated with suppressive function and inversely with the production of IFN-{gamma}, IL-6, IL-21 and IL-17. In contrast, the phenotype and function of FOXP3low MBP-specific T cells were adaptive and dependent on IL-6. The higher frequency of FOXP3high MBP-specific T cells was observed when IL-6 was neutralized in the culture of PBMC with MBP. The study provides new evidence that MBP-specific T cells are susceptible to pro-inflammatory cytokine milieu and act as either pro-inflammatory or regulatory T cells.

Keywords: forkhead/winged helix transcription factor gene (FOXP3), IL-6, MS, MBP, Tregs

Transmitting editor: C. J. Paige

Received 6 November 2008, accepted 14 September 2009.


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