Increased T-cell immunity against aquaporin-4 and proteolipid protein in neuromyelitis optica
Open Access
- 27 July 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 23 (9), 565-573
- https://doi.org/10.1093/intimm/dxr056
Abstract
In neuromyelitis optica (NMO), B-cell autoimmunity to aquaporin-4 (AQP4) has been shown to be essential. However, the role of T cells remains ambiguous. Here, we first showed an increase in CD69+ activated T cells in PBMCs during NMO relapses. Next, T-cell responses to AQP4 and myelin peptides were studied in 12 NM0 patients, 10 multiple sclerosis (MS) patients and 10 healthy subjects (HS). Four hours after adding 1 of 28 overlapping AQP4 peptides, a mixture of AQP4 peptides (AQP4-M) or one of six distinct myelin peptides to 2-day cultured PBMC, CD69 expression on CD4+ T cells was examined. Data were analyzed by paired t-test, frequency of samples with 3-fold increase of CD69 on CD4+ cells (fSI3) and mean stimulation index (mSI). The T-cell response to AQP4-M was significantly increased in NMO (fSI3 = 10/12, mSI = 5.50), with AQP4 (11–30) and AQP4 (91–110) representing the two major epitopes (AQP4 (11–30), fSI3 = 11/12, mSI = 16.0 and AQP4 (91–110), fSI3 = 11/12, mSI = 13.0). Significant but less extensive responses to these two epitopes were also observed in MS and HS. Significant reactivities against AQP4 (21–40), AQP4 (61–80), AQP4 (101–120), AQP4 (171–190) and AQP4 (211–230) were exclusively found in NMO. In addition, responses to AQP4 (81–100) were higher and more frequently detected in NMO, without reaching statistical significance. Interestingly, among the six myelin peptides studied, proteolipid protein (95–116) induced a significant T-cell response in NMO (fSI3 = 7/12, mSI = 4.60). Our study suggests that cellular as well as humoral responses to AQP4 are necessary for NMO development and that the immune response to myelin protein may contribute to disease pathogenesis.Keywords
This publication has 19 references indexed in Scilit:
- Fine specificity of antibodies against AQP4: Epitope mapping reveals intracellular epitopesJournal of Autoimmunity, 2011
- Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in miceBrain, 2010
- Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivoAnnals of Neurology, 2009
- Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosisBrain, 2007
- Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperationJCI Insight, 2006
- Revised diagnostic criteria for neuromyelitis opticaNeurology, 2006
- Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”Annals of Neurology, 2005
- IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channelThe Journal of Experimental Medicine, 2005
- IMMUNOLOGY OF MULTIPLE SCLEROSISAnnual Review of Immunology, 2005
- Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95–116 as an HLA-DR2,w15-associated determinantInternational Immunology, 1995