The Beta Chemokines CCL4 and CCL5 Enhance Adhesion of Specific CD4+ T Cell Subsets to Human Brain Endothelial Cells

Chemokines are key mediators of inflammation, acting as subset-specific chemoattractants and activators of leukocytes. In the present study we investigated the effects of chemokine concentration gradients on CD4 T cell (TC4) adhesion to human brain microvessel endothelial cells (HBMECs) in vitro. CC...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2004-04, Vol.63 (4), p.350-362
Main Authors: QUANDT, JACQUELINE, DOROVINI-ZIS, KATERINA
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain - metabolism
CD4-Positive T-Lymphocytes - immunology
Cell Adhesion - physiology
Cell Movement - physiology
Cells, Cultured
Chemokine CCL4
Chemokine CCL5
Chemokines, CC - metabolism
Electric Impedance
Endothelial Cells - metabolism
Humans
Lymphocyte Activation
Macrophage Inflammatory Proteins
Medical sciences
Microscopy, Immunoelectron
Neurology
Proteins - metabolism
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Summary:Chemokines are key mediators of inflammation, acting as subset-specific chemoattractants and activators of leukocytes. In the present study we investigated the effects of chemokine concentration gradients on CD4 T cell (TC4) adhesion to human brain microvessel endothelial cells (HBMECs) in vitro. CCL4 or CCL5 were placed in a double chamber chemotaxis system beneath confluent resting HBMEC monolayers or cultures co-incubated with TNF-α and IFN-γ to mimic an inflammatory milieu. Chemokines readily diffused across activated HBMEC monolayers while binding to the sub-endothelial regions, establishing a chemotactic and haptotactic gradient. Naïve or resting TC4 adhered poorly to resting HBMECs compared to memory or recently activated TC4, but all subsets adhered more readily to cytokine-treated HBMECs. Chemokine gradients (10–100 ng/ml) of both CCL4 and CCL5 significantly enhanced the adhesion of memory and recently activated TC4 to cytokine-treated HBMECs, as much as doubling adhesion in a manner that correlated with chemokine receptor expression. Neither chemokine influenced adhesion to resting HBMEC monolayers nor the adhesion of resting or naïve TC4. These findings emphasize the role and importance of CNS-derived β-chemokines in regulating the traffic of recently activated TC subsets (those previously localized to the CNS in vivo) across cytokine-activated cerebral endothelium in inflammatory diseases.
ISSN:0022-3069
1554-6578
DOI:10.1093/jnen/63.4.350