Selective CC chemokine receptor expression by central nervous system-infiltrating encephalitogenic T cells during...

Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T cell disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demyelination, and paralysis. Recent studies describing the relationship of chemokine expression with development of clinical disease have led to the hypothesis that distinct chemokine receptors corresponding to specific ligands are expressed by CNS-infiltrating antigen-specific encephalitogenic T cells as well as host-derived bystander T cells and monocytes. In an effort to study encephalitogenic T cell chemokine receptor expression, we examined CC chemokine receptor expression from resting, activated, and CNS-isolated CD4(+) T cells. CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, and CCR8 mRNA is expressed by normal CD4(+) T cells. In vitro activated T cells expressed CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, and CCR8 mRNA as well as CCR4. After EAE induction, CCR1 mRNA was expressed by donor-derived encephalitogenic and host-derived CD4(+) T cells isolated only from CNS and not from spleen. In vivo neutralization of the CCR1 ligand, macrophage inflammatory protein-1alpha (CCL3), resulted in less encephalitogenic CD4(+) T cell CNS infiltration. These results demonstrate the importance of CC chemokine receptor expression by CD4(+) encephalitogenic T cells for CNS infiltration and subsequent disease development.