Abstract
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T lymphocyte-mediated disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demy-elination, and paralysis. We previously demonstrated a role for chemokines in acute and relapsing EAE pathogenesis. Presently, we investigated the role of CC chemokine receptor 2 (CCR2) in acute EAE. CCR2(-/-) mice did not develop clinical EAE or CNS histopathology, and showed a significant reduction in T cell- and CNS-infiltrating CD45(high)F4/80+ monocyte subpopulations. Peripheral lymphocytes from CCR2(-/-) mice produced comparable levels of interferon-gamma (IFN-γ) and interleukin (IL)-2 in response to antigen-specific restimulation when compared with control mice. Adoptively transferred myelin oligodendrocyte glycoprotein 35-55-specific T cells lacking expression of CCR2 were able to induce EAE, whereas CCR2(-/-) recipients of wild-type T cells failed to develop disease. These results suggest that CCR2 expression on host-derived mononuclear cells is critical for disease induction.
Original language | English (US) |
---|---|
Pages (from-to) | 899-905 |
Number of pages | 7 |
Journal | Journal of Experimental Medicine |
Volume | 192 |
Issue number | 6 |
DOIs | |
State | Published - 2000 |
Keywords
- CC chemokine receptor 2
- CCL2
- Experimental autoimmune encephalomyelitis
- Knockout
- Multiple sclerosis