T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking.
It is believed that chemokines and their receptors are involved in trafficking of T-cells to the central nervous system (CNS). The aim of the current study was to define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine receptors associated with trafficking to sites of inflammation. Flow cytometry was used to detect chemokine receptor expression. We observed that CD3+T-cells in the CSF express a restricted array of inflammatory chemokine receptors, specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was independent of the presence of CNS inflammation, since comparable findings were obtained in patients with multiple sclerosis (MS) and individuals with non-inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T-cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells in the inflamed CNS.
Kivisäkk
P
P
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Trebst
C
C
Liu
Z
Z
Tucky
B H
BH
Sørensen
T L
TL
Rudick
R A
RA
Mack
M
M
Ransohoff
R M
RM
D000328:Adult; D017252:CD3 Complex / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D020278:Demyelinating Autoimmune Diseases, CNS / Q000134:cerebrospinal fluid / Q000276:immunology; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology*; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; C515187:CXCR3 protein, human; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens