Cutting edge: The silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis

D6, a promiscuous nonsignaling chemokine binding molecule expressed on the lymphatic endothelium, internalizes and degrades CC chemokines, and D6 ^-/- mice demonstrated increased cutaneous inflammation following topical phorbol ester or CFA injection. We report that D6-/- mice were unexpectedly resistant to the induction of experimental autoimmune encephalomyelitis due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35-55 in CFA, D6^-/- mice showed reduced spinal cord inflammation and demyelination with lower incidence and seventy of experimental autoimmune encephalomyelitis attacks as compared with D6^+/+ littermates. In adoptive transfer studies, MOG-primed D6^-/- T cells equally mediated disease in D6 ^+/+ or D6^-/- mice, whereas cells from D6^-/- mice transferred disease poorly to D6^+/- recipients. Lymph node cells from MOG-primed D6^-/- mice showed weak proliferative responses and made reduced IFN-γ but normal IL-5. CD11c⁺ dendritic cells accumulated abnormally in cutaneous immunization sites of D6^-/- mice. Surprisingly, D6, a "silent" chemokine receptor, supports immune response generation.