The level of B7 homologue 1 expression on brain DC is decisive for CD8 Treg cell recruitment into the CNS during EAE

Abstract

DC in the CNS have emerged as the major rate-limiting factor for immune invasion and subsequent neuroinflammation during EAE. The mechanism of how this is regulated by brain-localized DC remains unknown. Here, we describe the ability of brain-localized DC expressing B7-H1 molecules to recruit CD8+ T cells to the site of inflammation. Using intracerebral microinjections of B7-homologue 1-deficient DC, we demonstrate a substantial brain infiltration of CD8+ T cells displaying a regulatory phenotype (CD122+) and function, resulting in a decrease of EAE peak clinical values. The recruitment of regulatory-type CD8+ T cells into the CNS and the role of brain DC expressing B7-homologue 1 molecules in this process open up the possibility of DC-targeted therapeutic manipulation of neuroinflammatory diseases. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.