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(American Journal of Pathology. 2003;162:427-438.)
© 2003 American Society for Investigative Pathology

Regular Articles

CC Chemokine Receptor 8 in the Central Nervous System Is Associated with Phagocytic Macrophages

Corinna Trebst^*, Susan M. Staugaitis^*, Pia Kivisäkk^*, Don Mahad^*, Martha K. Cathcart, Barbara Tucky^*, Tao Wei^*, Mysore R. Sandhya Rani^*, Richard Horuk, Kenneth D. Aldape, Carlos A. Pardo^¶, Claudia F. Lucchinetti^||, Hans Lassmann^** and Richard M. Ransohoff^*

From the Departments of Neurosciences^* and Cell Biology, The Lerner Research Institute, and the Department of Neurology, the Mellen Center for Multiple Sclerosis Treatment and Research, the Cleveland Clinic Foundation, Cleveland, Ohio; Berlex Biosciences, Richmond, California; the Department of Pathology, University of California, San Francisco, California; the Department of Neurology,^¶ The Johns Hopkins University, Baltimore, Maryland; the Department of Neurology, || Mayo Clinic, Rochester, Minnesota; and the Brain Research Institute,^** University of Vienna, Vienna, Austria

CC chemokine receptor 8 (CCR8) has been detected in vitro on type 2 helper and regulatory lymphocytes, which might exert beneficial functions in multiple sclerosis (MS) and on macrophages and microglia, possibly promoting tissue injury in MS lesions. To discriminate the relevant expression pattern in vivo, we defined the cell types that expressed CCR8 in MS lesions and determined the relationship of CCR8 expression and demyelinating activity. CCR8 was not expressed on T cells but was associated with phagocytic macrophages and activated microglia in MS lesions and directly correlated with demyelinating activity. To identify factors associated with CCR8 expression, the study was extended to other central nervous system (CNS) pathologies. CCR8 was consistently expressed on phagocytic macrophages and activated microglia in stroke and progressive multifocal leukoencephalopathy, but not expressed on microglia in pathologies that lacked phagocytic macrophages such as senile change of the Alzheimer’s type. CCR8 was up-regulated by macrophage differentiation and activating stimuli in vitro. In summary CNS CCR8 expression was associated with phagocytic macrophages and activated microglial cells in human CNS diseases, suggesting that CCR8 may be a feasible target for therapeutic intervention in MS. CCR8 expression may also indicate a selective program of mononuclear phagocyte gene expression.

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