van Nierop GP, Janssen M, Mitterreiter JG, van de Vijver DA, de Swart RL, Haagmans BL, Verjans GM, Hintzen RQ. Intrathecal CD4+ and CD8+ T cell responses to endogenously synthesized candidate disease-associated human autoantigens in multiple sclerosis patients. Eur J Immunol. 2015 Oct 28. doi: 10.1002/eji.201545921. [Epub ahead of print]
Multiple sclerosis (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 (MBP), proteolipid protein, ATP-dependent potassium channel KIR4.1, S100 calcium-binding protein B, contactin-2 and neurofascin. Transduced BLCL 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.
So yesterday we had the B cell autoimmunity and not to be outdone we get T cell autoimmunity. In this study they get B cells to express a number of antigens and then see if T cells present in the CNS respond to them and surprise, surprise they don’t respond to the common myelin antigens although they can be stimulated with a mitogenic (stimulates T cells independent of there T cell receptor). About twenty years ago this type of study was done on blood cells and they found that T cells did not respond to myelin antigens but responded to alpha B crystallin which wasn’t examined here. But yesterday we were showing B cells respond to nerves and glia and not myelin and today we see that T cells are not responding to myelin, so some ideas of autoimmunity masy need abit of a think. However, many cells in the CNS will be attracted in by the inflammatory environment and the majority have nothing to do with disease. Furthermore we have to remember the target in MS is the oligodendrocyte, but it ain’t MBP