Cerebral leucocyte infiltration in lupus-prone MRL/MpJ-fas lpr mice--roles of intercellular adhesion molecule-1 and P-selectin

The autoimmune disease which affects MRL/MpJ-fas(lpr) mice results in cerebral leucocyte recruitment and cognitive dysfunction. We have previously observed increased leucocyte trafficking in the cerebral microcirculation of these mice; however, the types of leucocytes recruited have not been analysed thoroughly, and the roles of key endothelial adhesion molecules in recruitment of these leucocytes have not been investigated. Therefore the aim of this study was to classify the phenotypes of leucocytes present in inflamed brains of MRL/MpJ-fas(lpr) mice, and dissect the roles of endothelial adhesion molecules in their accumulation in the brain. Immunohistochemical analysis revealed significant leucocyte infiltration in the brains of 16- and 20-week-old MRL/MpJ-fas(lpr) mice, affecting predominantly the choroid plexus. Isolation of brain-infiltrating leucocytes revealed that lymphocytes and neutrophils were the main populations present. The CD3(+) lymphocytes in the brain consisted of similar proportions of CD4(+), CD8(+) and CD4(-)/CD8(-)[double negative (DN)] populations. Assessment of MRL/MpJ-fas(lpr) mice deficient in endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) or P-selectin indicated that cerebral leucocyte recruitment persisted in the absence of these molecules, with only minor changes in the phenotypes of infiltrating cells. Together these data indicate that the brains of MRL/MpJ-fas(lpr) mice are affected by a mixed leucocyte infiltrate, of which the unusual DN lymphocyte phenotype contributes a substantial proportion. In addition, endothelial adhesion molecules ICAM-1 and P-selectin, which modulate survival of MRL/MpJ-fas(lpr) mice, do not markedly inhibit leucocyte entry into the central nervous system.