Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood‐brain barrier suggests their involvement in G‐protein‐dependent …

C Alt, M Laschinger… - European journal of …, 2002 - Wiley Online Library
C Alt, M Laschinger, B Engelhardt
European journal of immunology, 2002Wiley Online Library
Migration of autoaggressive T cells across the blood‐brain barrier (BBB) is critically involved
in the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for
multiple sclerosis. The direct involvement of chemokines in this process was suggested by
our recent observation that G‐protein‐mediated signaling is required to promote adhesion
strengthening of encephalitogenic T cells on BBB endothelium in vivo. To search for
chemokines present at the BBB, we performed in situ hybridizations and …
Abstract
Migration of autoaggressive T cells across the blood‐brain barrier (BBB) is critically involved in the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The direct involvement of chemokines in this process was suggested by our recent observation that G‐protein‐mediated signaling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo. To search for chemokines present at the BBB, we performed in situ hybridizations and immunohistochemistry and found expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in venules surrounded by inflammatory cells. Their expression was paralleled by the presence of their common receptor CCR7 in inflammatory cells in brain and spinal cord sections of mice afflicted with EAE. Encephalitogenic T cells showed surface expression of CCR7 and the alternative receptor for CCL21, CXCR3. They specifically chemotaxed towards both CCL19 or CCL21 in a concentration dependent and pertussis toxin‐sensitive manner comparable to naive lymphocytes in vitro. Binding assays on frozen sections of EAE brains demonstrated a functional involvement of CCL19 and CCL21 in adhesion strengthening of encephalitogenic T lymphocytes to inflamed venules in the brain. Taken together our data suggest that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue are involved in T lymphocyte migration into the immunoprivileged central nervous system during immunosurveillance and chronic inflammation.
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