Functional Expression of Chemokine Receptor CCR5 on CD4+ T Cells during Virus-Induced Central Nervous System Disease

AUTOR(ES)

Glass, William G.

FONTE

American Society for Microbiology

RESUMO

Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). CD4+ T cells are important in amplifying demyelination by attracting macrophages into the central nervous system (CNS) following viral infection; however, the mechanisms governing the entry of these cells into the CNS are poorly understood. The role of chemokine receptor CCR5 in trafficking of virus-specific CD4+ T cells into the CNS of MHV-infected mice was investigated. CD4+ T cells from immunized CCR5+/+ and CCR5−/− mice were expanded in the presence of the immunodominant epitope present in the MHV transmembrane (M) protein encompassing amino acids 133 to 147 (M133-147). Adoptive transfer of CCR5+/+-derived CD4+ T cells to MHV-infected RAG1−/− mice resulted in CD4+-T-cell entry into the CNS and clearance of virus from the brain. These mice also displayed robust demyelination correlating with macrophage accumulation within the CNS. Conversely, CD4+ T cells from CCR5−/− mice displayed an impaired ability to traffic into the CNS of MHV-infected RAG1−/− recipients, which correlated with increased viral titers, diminished macrophage accumulation, and limited demyelination. Analysis of chemokine receptor mRNA expression by M133-147-expanded CCR5−/−-derived CD4+ T cells revealed reduced expression of CCR1, CCR2, and CXCR3, indicating that CCR5 signaling is important in increased expression of these receptors, which aid in trafficking of CD4+ T cells into the CNS. Collectively these results demonstrate that CCR5 signaling is important to migration of CD4+ T cells to the CNS following MHV infection.

Documentos Relacionados

• A Central Role for CD4+ T Cells and RANTES in Virus-Induced Central Nervous System Inflammation and Demyelination
• Dynamics of CCR5 Expression by CD4+ T Cells in Lymphoid Tissues during Simian Immunodeficiency Virus Infection
• CD4+ T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation
• Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4+ and CD8+ T Cells and Viral Persistence
• Treatment of encephalomyocarditis virus-induced central nervous system demyelination with monoclonal anti-T-cell antibodies.