CXCR3 expression in human central nervous system diseases

The CXCR3 chemokine receptor, expressed on activated T lymphocytes, is seen within the central nervous system (CNS) in inflammatory conditions where a T-cell response is prominent. However. the distribution of CXCR3 in parenc hymal CNS cells is unknown. Using a monoclonal antibody against CXCR3 and p ost-mortem tissue of patients with and without CNS pathology, we have deter mined its expression pattern. CXCR3 was found in subpopulations of cells mo rphologically consistent with astrocytes, particularly reactive astrocytes, and in cerebellar Purkinje cells. It was also detected in arterial endothe lial and smooth muscle cells, particularly in areas associated with atheros clerotic plaques. CXCR3-positive astrocytes were particularly prominent in the UNS of HIV-positive patients, in patients with Multiple Sclerosis (MS), in ischaemic infarcts and in astrocytic neoplasms. Immunofluorescence stud ies of mixed adult primary glial cultures and fetal glial cultures also sho wed expression of CXCR3 in astrocytes. CXCR3 mRNA was detected in Purkinje cells by in situ hybridization with a CXCR3-specific probe. Thus, the predo minant expression of CXCR3 in reactive astrocytes may indicate that it play s a role in the development of reactive gliosis in a variety of infectious, inflammatory, vascular and neoplastic processes in the CNS. The relationsh ip between CXCR3 expression in astrocytes to its expression in Purkinje cel ls, endothelial cells and smooth muscle cells is yet to be determined.