Exogenous antigen containing perivascular phagocytes induce a non-encephalitogenic extravasation of primed lymphocytes

Recent evidence suggests that T-lymphocyte extravasation and CNS-parenchyma l infiltration during autoimmune disease might be regulated by antigen-pres enting (ED2(+)) cerebral/spinal perivascular phagocytes (CPP/SPP). Since th e massive erythrocytic and leukocytic infiltrates in the CNS of rats with e xperimental allergic encephalomyelitis do not allow a precise differentiati on between CPP/SPP and the invading cells in the Virchow-Robin space, we de veloped a new immune-response model whereby the extravasation of T-lymphocy tes was not followed by other blood cells. Adult Lewis rats were sensitized to horseradish peroxidase (HRP). Subsequent intracerebroventricular (i.c.v .) injections of HRP and/or Fluoro-Emerald (FE) served to: (1) challenge th e primed T-lymphocytes and (2) label the CPP/SPP for additional immunocytoc hemical analysis. We found that 24 h and 3 days after single, double, or tr iple antigen boosting T-lymphocytes (R73(+), W3/25(+), OX50(+)) entered the Virchow-Robin space but did not break through the astrocytic glia limitans . Instead they adhered to HRP-containing activated CPP/SPP (mabs OX-6(+), S ILK6(+), CD40(+), CD80(+), CD86(+)). This selective contact was mediated ne ither by cell adhesion molecules (P-selectin, ICAM-1, VCAM-1), nor promoted by chemokine receptors (CCR1, CCR5) or chemokines (monocyte chemoattractan t protein (MCP)-1, MIP-1 alpha, MIP-1 beta, RANTES). This non-inflammatory, but antigen-dependent lymphocyte extravasation provides optimal conditions to further study the CNS immune response. (C) 2001 Elsevier Science B.V. A ll rights reserved.