The silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis (130.33)

Abstract

Abstract D6, a promiscuous non-signaling chemokine binding molecule expressed on lymphatic endothelium, internalizes and degrades CC chemokines, and D6−/− mice demonstrated increased cutaneous inflammation following topical phorbol ester or complete Freund’s adjuvant (CFA) injection. We report that D6−/− mice were unexpectedly resistant to induction of experimental autoimmune encephalomyelitis (EAE), 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 severity of EAE attacks, compared to D6+/+ littermates. In adoptive transfer studies, MOG-primed D6+/- T cells equally mediated disease in D6+/+ or D6−/− mice, while 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-gamma, 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.