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

• Published in: Clinical and experimental immunology Vol. 129; no. 3; pp. 510 - 518
• Main Authors: KIVISÄKK, P., TREBST, C., LIU, Z., TUCKY, B. H., SØRENSEN, T. L., RUDICK, R. A., MACK, M., RANSOHOFF, R. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2002; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Biological and medical sciences; CD3 Complex - chemistry; CD4-Positive T-Lymphocytes - immunology; Central Nervous System - immunology; cerebrospinal fluid T‐cells multiple sclerosis chemokine receptors; Chemotaxis, Leukocyte; Clinical Studies; Demyelinating Autoimmune Diseases, CNS - cerebrospinal fluid; Demyelinating Autoimmune Diseases, CNS - immunology; Female; Humans; Leukocyte Common Antigens - analysis; Male; Medical sciences; Middle Aged; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Receptors, CCR5 - metabolism; Receptors, Chemokine - metabolism; Receptors, CXCR3; T-Lymphocytes - immunology; Human; Nervous system diseases; Multiple sclerosis; Pathogenesis; Central nervous system; Inflammation; Chemokine receptor; Cerebrospinal fluid; Inflammatory disease; CCR5 chemokine receptor; Immunological investigation; CCR6 chemokine receptor; Central nervous system disease; T-Lymphocyte; CXCR5 chemokine receptor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2002.01947.x

SUMMARY 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.