MS patients also have increased

antibody levels to these antigens. The target cells are spontaneously growing peripheral blood mononuclear cells (PBMCs) of B cell lineage, expressing human endogenous retrovirus HERV epitopes on their surface. Polyclonal antibodies against defined peptides in the Env- and Gag-regions of the HERVs were raised in rabbits and used in antibody-dependent cell-mediated MK2206 cytotoxicity (ADCC) -assays. Rituximab® (Roche), a chimeric monoclonal antibody against CD20 expressed primarily on B cells, was used as control antibody. Without antibodies this system is suitable for analyses of natural killer cell activity. In optimization of the assay we have used effector lymphocytes from healthy donors. The most effective effector cells are CD56+ cells. CD8+ T cells also express CD107a in ADCC. Using the adapted assay, we demonstrate

significant ADCC activity to target cells expressing HERV epitopes, and additionally a low level of NK activity. The neurological disease multiple sclerosis (MS) is characterized by inflammation in different locations in the central nervous system (CNS), resulting in lesions with cell death and scar formation in both myelin sheaths and neurones. The initiating cause(s) of this process is unknown. The observed cell death could be caused by apoptosis (internal signals) or Small molecule library by external, possibly immune-mediated factors with cytotoxicity, caused by different effector cells and effector molecules, among the potential candidates.

We have shown previously that spontaneously growing cell cultures originating from peripheral blood mononuclear cells (PBMCs) from MS patients express human endogenous retroviruses (HERV)-H and HERV-W epitopes on their surface membranes [1]. These HERV epitopes are also expressed on the surfaces of PBMCs from MS patients with expression levels linked to Isotretinoin different stages of the disease. These epitopes may trigger both natural killer (NK) cell activity and antibody production, the latter resulting in antibody-dependent cell-mediated cytotoxicity (ADCC). Activation of cytotoxic T cells (CD8+ and γδ T cells) may also occur, with a resulting continuum of HERV-related cytotoxic effector mechanisms that could play a role in development of the disease. The expressed epitopes could be the target, or part of the targets, for cytotoxic effectors, making testing of the different cytotoxic reactions highly relevant. For many years, measuring of 51Cr-release from labelled target cells has been the gold standard for such assays, due particularly to the consistency and reproducibility of the results.