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Abstract

Our study1 referred to by Professor Pender describes a very early stage in the formation of new multiple sclerosis (MS) lesions characterized by the presence of broad areas of palely staining (but still largely intact) myelin sheaths, containing apoptotic oligodendrocytes and activated microglia, but few or no myelin phagocytes or lymphocytes. The absence of T lymphocytes in the immediate vicinity of apoptotic oligodendrocytes is especially significant, because such changes have not been reported in any form of the animal model, experimental allergic encephalomyelitis (EAE). As noted by ourselves and Dr Trapp,2 this raises the possibility of important differences in the pathogenesis of these two diseases. Professor Pender suggests that steroid administration shortly before death may have cleared the central nervous system (CNS) of T cells; this possibility can be ruled out first by the fact that not all seven patients (in whom apoptotic lesions were identified) received such treatment, and second by the presence of numerous lymphocytes in zones of active phagocytosis adjacent to or contiguous with areas exhibiting prominent oligodendrocyte apoptosis in each of the 10 apoptotic lesions described. In the patient with the 17-hour symptomatic lesion, we described an absence of lymphocytes in zones of oligodendrocyte apoptosis, but relatively numerous CD4, CD8, and especially CD45RO+ T cells together with myelin phagocytes elsewhere in the lesion.1 Also as noted in our study, the findings were consistent in each of the nine other apoptotic lesions described. Our findings argue strongly against direct T-cell–mediated destruction of oligodendrocytes in early MS lesions. Rather, they suggest that dissolution of myelin by macrophages is largely or entirely scavenging activity directed against dead myelin sheaths, that is, plasma membrane of apoptotic oligodendrocytes. As noted by Professor Pender, however, our results do not rule out antibody or other humoral factors as effectors of oligodendrocyte apoptosis in early MS lesions. John W. Prineas MB, BS*, Michael H. Barnett MB, BS*, * Department of Medicine, The University of Sydney, Sydney, Australia.