EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - QUALITATIVE AND SEMIQUANTITATIVE DIFFERENCES IN HEAT-SHOCK PROTEIN-60 EXPRESSION IN THE CENTRAL-NERVOUS-SYSTEM

The factors that contribute to disease progression in multiple scleros is (MS) and its animal model, experimental autoimmune encephalomyeliti s (EAE), are not known. In this study, we have tested the hypothesis t hat inflammation in the central nervous system (CNS) is associated wit h altered expression of heat shock proteins (hsp) that may function as a target in the development of chronic disease. In normal mouse spina l cord, hsp 60 immunoreactivity was localized exclusively to its const itutive site in mitochondria. In animals with acute EAE, lesions were accentuated by increased expression of hsp 60, primarily by infiltrati ng cells. In chronic EAE, hsp 60 was found predominantly on CNS compon ents, particularly oligodendrocytes and astrocytes. In both acute and chronic lesions, hsp 60 was located in the cytoplasm of cells, but in non-lesion areas, it was mitochondrial. By semiquantitative Western bl otting, hsp 60 in normal mouse spinal cord (n = 6) was 0.99 +/- 0.09% of total protein. In acute EAE (n = 6), the value was 1.08 +/- 0.1%, a nd in chronic EAE (n = 8), 1.39 +/- 0.39%. FAGS analysis showed that a subpopulation of CD3(+) cells expressed hsp 60 on the cell surface, a n observation confirmed by cell surface labeling and immunoprecipitati on. In chronic EAE lesions, gamma delta T cells colocalized with areas of increased hsp 60 immunoreactivity. The results support the conclus ion that development of autoimmune-directed inflammation in the CNS is associated with differences in hsp 60 expression that may act as an a dditional target and/or modulator of the immune response.