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Lymphocytic choriomeningitis virus infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood-brain barrier breakdown and convulsive seizures. Although lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes (CTLs) are essential for disease, their mechanism of action is not known. To gain insights into disease pathogenesis, we observed the dynamics of immune cells in the meninges by two-photon microscopy. Here we report visualization of motile CTLs and massive secondary recruitment of pathogenic monocytes and neutrophils that were required for vascular leakage and acute lethality. CTLs expressed multiple chemoattractants capable of recruiting myelomonocytic cells. We conclude that a CD8(+) T-cell-dependent disorder can proceed in the absence of direct T-cell effector mechanisms and rely instead on CTL-recruited myelomonocytic cells.

Original publication

DOI

10.1038/nature07591

Type

Journal article

Journal

Nature

Publication Date

08/01/2009

Volume

457

Pages

191 - 195

Keywords

Acute Disease, Animals, Blood-Brain Barrier, Central Nervous System, Lymphocytic choriomeningitis virus, Meninges, Meningitis, Viral, Mice, Mice, Inbred C57BL, Monocytes, Neutrophil Infiltration, Neutrophils, Seizures, Stromal Cells, T-Lymphocytes, Cytotoxic