EBV-specific CD8 cells in CSF

van Nierop GP, Mautner J, Mitterreiter JG, Hintzen RQ, Verjans GM. Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic Epstein-Barr virus proteins.Mult Scler. 2015 Jun 3. pii: 1352458515588581. [Epub ahead of print]

BACKGROUND:The association between Epstein-Barr virus (EBV) and multiple sclerosis (MS) may involve intrathecal EBV-specific T-cell responses targeting the virus or indirectly, autoantigens.
OBJECTIVE:Compare the prevalence and fine-specificity of EBV-specific T-cells in the cerebrospinal fluid (CSF) of patients with MS (n = 12), clinically-isolated syndrome (CIS) (n = 17) and other neurological diseases (OND) (n = 13).
METHODS:Intrathecal EBV-specific T-cell reactivity was assayed using CSF-derived T-cell lines (CSF-TCL) and autologous EBV-transformed B-cells (autoBLCL) as antigen-presenting cells (APC). EBV proteins recognized by autoBLCL-specific CD8 T-cells were identified using human leukocyte antigen class I (HLA-I)-negative monkey cells as artificial APC, co-transfected with 59 different EBV genes and the corresponding patient's HLA-I alleles that were involved in autoBLCL T-cell reactivity. Reactivity towards the MS-associated autoantigen αB-crystallin (CRYAB) was determined analogously.
RESULTS:CSF-TCL from CIS and MS patients had significantly higher frequencies of autoBLCL-reactive CD4 T-cells, compared to the OND patients. CIS patients also had significantly higher autoBLCL-reactive CD8 T cells, which correlated with reactive CD4 T-cell frequencies. AutoBLCL-specific CD8 T-cell responses of four CSF-TCL analyzed in detail were oligoclonal and directed to lytic EBV proteins, but not CRYAB endogenously expressed by autoBLCL.
CONCLUSIONS:Enhanced intrathecal autoBLCL-specific T-cell reactivity, selectively directed towards lytic EBV proteins in two CSF-TCL, suggested a localized T-cell response to EBV in patients with MS. Our data warrant further characterization of the magnitude and breadth of intrathecal EBV-specific T-cell responses in larger patient cohorts.
EBV immortalises B cells and so you can infect B cells to make a cell line to present antigen so you can make a T cell line by stimulating it with its target antigen. They then used these T cells to work out which protein was being recognised by stimulating them with mock antigen presenting cells expressing different antigens. They found more EBV reactive CD4 T cells in the CSF of MSers an more CD8 cells into CISers. There responded to EBV proteins. Is this the main target.

Rebound occurs after withdrawal of natalizumab and the cells arriving in the brain at this time are going to contain the cells that cause relapse in MS. What are these cells reactive to?  EBV, CRYAB or myelin proteins

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