Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

• Published in: The Journal of clinical investigation Vol. 103; no. 6; pp. 807 - 815
• Main Authors: Sørensen, T L, Tani, M, Jensen, J, Pierce, V, Lucchinetti, C, Folcik, V A, Qin, S, Rottman, J, Sellebjerg, F, Strieter, R M, Frederiksen, J L, Ransohoff, R M
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.03.1999
• Subjects: Acute Disease; Adult; Aged; Aged, 80 and over; Central Nervous System - chemistry; Central Nervous System - immunology; Chemokine CCL5 - cerebrospinal fluid; Chemokine CXCL10; Chemokine CXCL9; Chemokines - cerebrospinal fluid; Chemokines, CXC - cerebrospinal fluid; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Multiple Sclerosis - etiology; Multiple Sclerosis - immunology; Receptors, CCR5; Receptors, Chemokine - analysis; Receptors, Cytokine - analysis; T-Lymphocytes - chemistry; T-Lymphocytes - immunology
• ISSN: 0021-9738
• DOI: 10.1172/jci5150

Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma-inducible protein of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine-chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.