NK cell-mediated lysis of autologous human oligodendrocytes

Although considered an autoimmune disease, the mechanisms underlying oligod endrocyte (OL)/myelin injury in multiple sclerosis (MS) remain to be establ ished. We utilized in vitro assays to demonstrate that human OLs, as well a s other glial elements (astrocytes, microglia), were susceptible to injury mediated by peripheral blood-derived mononuclear cell preparations (MNCs) e nriched for natural killer (NK cells) by depleting CD3(+) +/- CD19(+) cells through use of either magnetic beads or cell sorting. Cytotoxic effects of the NK cell-enriched effecters were dependent on pre-exposure of these cel ls to IL-2. Furthermore, we found that autologous OLs were as susceptible t o injury mediated by IL-2 activated NK cells as were heterologous OLs. In c ontext of the tissue injury that occurs in MS, our results suggest that the inflammatory milieu in MS lesions could provide conditions required for NK cell activation and that such effector cells can bypass the putative prote ctive effects of self-MHC class I molecules that may be expressed on OLs. ( C) 2001 Elsevier Science B.V. All rights reserved.