REGULATION OF LYMPHOCYTE HOMING INTO THE BRAIN DURING VIRAL ENCEPHALITIS AT VARIOUS STAGES OF INFECTION

The passage of circulating lymphocytes into the central nervous system (CNS) during acute viral encephalitis was studied in vivo using fluor escently labeled cells inoculated into Sindbis virus (SV)-infected mic e. Donor lymphocytes were detected in the brains of recipient animals when mononuclear cells were isolated from the CNS and screened by flow cytometry. The magnitude of this accumulation related to the duration of encephalitis in recipient mice and to the activation state of the inoculated cells. While Ag specificity did not influence lymphocyte en try into the inflamed CNS at any stage of infection, SV-immune cells w ere retained selectively within the brains of infected animals compare d with cells of an irrelevant specificity, Coincident with the onset o f CNS inflammation, ICAM-1 and VCAM-1 were up-regulated on cerebrovasc ular endothelium. Lymphocyte entry into the brains of infected animals during maximal inflammation could be inhibited by pretreating inocula ted cells with Abs that blocked LFA-1, but not with those that blocked VLA-4 or down-regulated CD44. None of these reagents prevented lympho cyte entry into the brain at the onset of inflammation, suggesting tha t the earliest recruited cells utilize presently uncharacterized recep tor-ligand interactions. These data show that the degree of existing i nflammation and the activation state of circulating cells, but not the ir Ag specificity, influence lymphocyte recruitment into the brain dur ing SV encephalitis. While CNS homing can be blocked with Abs against known adhesion molecules during peak inflammation, lymphocyte entry in to the brain during early infection remains poorly characterized.