Regulatory and pro-inflammatory phenotypes of myelin basic protein-autoreactive T cells in multiple sclerosis.
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 MBP(83-99)-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 FOXP3(low) MBP-specific T cells were adaptive and dependent on IL-6. The higher frequency of FOXP3(high) 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.
Hong
Jian
J
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. jhong@bcm.edu
Li
Haiyan
H
Chen
Meiyue
M
Zang
Ying C Q
YC
Skinner
Sheri M
SM
Killian
James M
JM
Zhang
Jingwu Z
JZ
D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D004676:Myelin Basic Protein