CXCR3 marks CD4+ memory T lymphocytes that are competent to migrate across a human brain microvascular endothelial cell layer.
Chemokines and their receptors may be implicated in leukocyte ingress into brain during inflammation observed during the course of multiple sclerosis (MS). To address receptor modulation on CD4+ memory T lymphocytes during diapedesis, we used an in vitro model of the blood-brain barrier (BBB). We found that only memory (CD45RO+) cells transmigrated and type 3 CXC chemokine receptor (CXCR3) was enriched on transmigrated cells. CXCR3 depletion of the input population did not affect transmigration capability. CXCR3 reemerged on CXCR3 depleted cells independently of endothelial cell exposure, but was susceptible to incubation at 4 degrees C, indicating receptor recycling. We propose that CXCR3 serves as a surface marker for cells that have the capacity to cross the BBB, but does not play an essential role in extravasation.
Callahan
Melissa K
MK
Department of Neurosciences, Cleveland Clinic Foundation, NC 30 Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Williams
Katherine A
KA
Kivisäkk
Pia
P
Pearce
Donna
D
Stins
Monique F
MF
Ransohoff
Richard M
RM
D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D017097:Electric Impedance; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007156:Immunologic Memory; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
C515187:CXCR3 protein, human; D018925:Chemokines; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein