Exogenous antigen containing perivascular phagocytes induce a non-encephalitogenic extravasation of primed lymphocytes.
Recent evidence suggests that T-lymphocyte extravasation and CNS-parenchymal infiltration during autoimmune disease might be regulated by antigen-presenting (ED2(+)) cerebral/spinal perivascular phagocytes (CPP/SPP). Since the massive erythrocytic and leukocytic infiltrates in the CNS of rats with experimental allergic encephalomyelitis do not allow a precise differentiation between CPP/SPP and the invading cells in the Virchow-Robin space, we developed a new immune-response model whereby the extravasation of T-lymphocytes 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 the primed T-lymphocytes and (2) label the CPP/SPP for additional immunocytochemical analysis. We found that 24 h and 3 days after single, double, or triple 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(+), SILK6(+), CD40(+), CD80(+), CD86(+)). This selective contact was mediated neither by cell adhesion molecules (P-selectin, ICAM-1, VCAM-1), nor promoted by chemokine receptors (CCR1, CCR5) or chemokines (monocyte chemoattractant protein (MCP)-1, MIP-1alpha, MIP-1beta, RANTES). This non-inflammatory, but antigen-dependent lymphocyte extravasation provides optimal conditions to further study the CNS immune response.
Walther
M
M
Institut I für Anatomie der Universität zu Köln, Joseph-Stelzmann-Strasse 9, D-50931, Cologne, Germany.
Popratiloff
A
A
Lachnit
N
N
Hofmann
N
N
Streppel
M
M
Guntinas-Lichius
O
O
Neiss
W F
WF
Angelov
D N
DN
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000276:immunology*; D002448:Cell Adhesion; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006735:Horseradish Peroxidase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008214:Lymphocytes / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008297:Male; D010586:Phagocytes / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
C515302:Ccr1 protein, rat; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D006735:Horseradish Peroxidase