OPTIC-NERVE DEGENERATION INDUCES THE EXPRESSION OF MHC ANTIGENS IN THE RAT VISUAL-SYSTEM

The brain has long been considered to be an immunologically privileged site. However, privilege is not absolute, as has been shown by the in ability of foreign tissue grafts to survive indefinitely in the brain. The rejection of this tissue is accompanied by the upregulation of ma jor histocompatibility complex (MHC) antigen expression. Therefore it is essential to define conditions that influence the expression of the se antigens in the brain, especially since such a definition may furth er the understanding of disease processes that lead to the autoimmune destruction of the central nervous system. Here we show that both MHC class I and class II antigens are expressed within 1 or 2 days of eye removal by cells showing the morphological characteristics of microgli a. Expression is seen along the optic pathway and within the brainstem centers to which optic axons project. In the early stages of the reac tion, MHC class I antigen expression is seen throughout the optic path way, including the terminal distribution areas of the subcortical visu al centers, while MHC cells class II are localised mainly to degenerat ing myelinated fiber systems. These changes are not accompanied by any alteration in the integrity of the blood-brain barrier. During the se cond week postlesion, class I positive cells are found beyond the conf ines of the degenerating pathways, while class II positive cells are s een within regions such as the stratum griseum superficiale of the sup erior colliculus, where few myelinated axons are present. There is sub sequent diminution of MHC positive cells, but a small number of cells are still seen 60 days post-lesion. Focal lesions within the eye show that at early survival times, while class I MHC positive cells are dis tributed throughout the nerve, class II positive cells are largely abs ent from the unmyelinated segment of the nerve. Retrograde changes in the retina after nerve section are accompanied only by MHC class I ant igen expression. These observations show that neural degeneration is a ccompanied by a rigid sequence of events involving expression of MHC a ntigens by microglia. If foreign antigens were present in the brain wh ile these events were taking place, it is possible that such antigens would be recognised and destroyed by the host immune system. (C) 1993 Wiley-Liss, Inc.