Migration of i.c. injected BMDCs from brain to deep cervical lymph nodes is CCR7 dependent but does not promote EAE disease progression (CCR1P.244)

Abstract

Abstract Cell-mediated antigen (Ag) drainage from the central nervous system (CNS) is incompletely understood. In other organs, Ag-presenting cells—such as dendritic cells (DCs)—migrate from organ tissue through lymphatics to draining lymph nodes (dLNs); however, classical lymphatic vessels are not found in the CNS and few migratory tissue DCs populate neuropil. In the context of neuroinflammation associated with experimental autoimmune encephalomyelitis (EAE), intracerebral (i.c.) injection of myelin peptide-loaded bone marrow (BM)DCs exacerbates disease, suggesting that increasing the number of CNS-DCs promotes EAE progression. However, whether CNS-infiltrating DCs transport Ag to dLNs for T cell priming or restimulate myelin-specific effector T cells in situ within developing CNS inflammatory lesions is unknown. Since migration of i.c. injected BMDCs to dLNs is pertussis toxin sensitive—and thus likely regulated by G proteins/ chemokine receptors—we sought to identify key chemokine receptors that govern DC migration from CNS to dLN. Here we report that 1) CCR7+/+ but not CCR7-/- BMDCs appear in dLNs after i.c. injection, 2) CCR7-/- DCs accumulate in CNS but not dLNs during EAE compared to CCR7+/+ DCs, 3) CCR7 is not necessary for i.c. injected BMDCs to exacerbate EAE, and 4) ablation of CCR7+/+ DCs during onset of EAE leads to increased CNS T cell cytokine production. These data suggest CCR7-dependent DC migration from CNS to dLN might regulate T cell responses in early EAE.