Intrathecal CD4+ and CD8+ T-cell responses to endogenously synthesized candidate disease-associated human autoantigens in multiple sclerosis patients
European Journal of Immunology , Volume 46 - Issue 2 p. 347- 353
MS pathology is potentially orchestrated by autoreactive T cells, but the antigens recognized remain unknown. A novel APC/T-cell platform was developed to determine intrathecal CD4+ and CD8+ T-cell responses to candidate MS-associated autoantigens (cMSAg) in clinically isolated syndrome (CIS, n = 7) and MS (n = 6) patients. Human cMSAg encoding open reading frames (n = 8) were cloned into an Epstein-Barr virus (EBV)-based vector to express cMSAg at high levels in EBV-transformed B-cells (BLCLs). Human cMSAg cloned were myelin-associated and -oligodendrocyte glycoprotein, myelin basic protein, proteolipid protein, ATP-dependent potassium channel ATP-dependent inwards rectifying potassium channel 4.1, S100 calcium-binding protein B, contactin-2, and neurofascin. Transduced BLCLs were used as autologous APC in functional T-cell assays to determine cMSAg-specific T-cell frequencies in cerebrospinal fluid derived T-cell lines (CSF-TCLs) by intracellular IFN-γ flow cytometry. Whereas all CSF-TCL responded strongly to mitogenic stimulation, no substantial T-cell reactivity to cMSAg was observed. Contrastingly, measles virus fusion protein-specific CD4+ and CD8+ T-cell clones, used as control of the APC/T-cell platform, efficiently recognized transduced BLCL expressing their cognate antigen. The inability to detect substantial T-cell reactivity to eight human endogenously synthesized cMSAg in autologous APC do not support their role as prominent intrathecal T-cell target antigens in CIS and MS patients early after onset of disease.
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van Nierop, G.P, Janssen, M, Mitterreiter, J.G, van de Vijver, D.A.M.C, de Swart, R.L, Haagmans, B.L, … Hintzen, R.Q. (2016). Intrathecal CD4+ and CD8+ T-cell responses to endogenously synthesized candidate disease-associated human autoantigens in multiple sclerosis patients. European Journal of Immunology, 46(2), 347–353. doi:10.1002/eji.201545921