CCR7 on CD4+ T Cells Plays a Crucial Role in the Induction of Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS. Myelin-specific CD4⁺ Th lymphocytes are known to play a major role in both MS and its animal model experimental autoimmune encephalomyelitis (EAE). CCR7 is a critical element for immune cell trafficking and recirculation, that is, lymph node homing, under homeostatic conditions; blocking CCR7⁺ central memory cells from egress of lymph nodes is a therapeutic approach in MS. To define the effect of CD4⁺ T cell-specific constitutive deletion of CCR7 in the priming and effector phase in EAE, we used an active EAE approach in T cell reconstituted Rag1^-/- mice, as well as adoptive transfer EAE, in which mice received in vitro-primed CCR7^-/- or CCR7^+/+ myelin Ag TCR-transgenic 2d2 Th17 cells. Two-photon laser scanning microscopy was applied in living anesthetized mice to monitor the trafficking of CCR7-deficient and wild-type CD4⁺ T cells in inflammatory lesions within the CNS. We demonstrate that CD4⁺ T cell-specific constitutive deletion of CCR7 led to impaired induction of active EAE. In adoptive transfer EAE, mice receiving in vitro-primed CCR7^-/- 2d2 Th17 cells showed similar disease onset as mice adoptively transferred with CCR7^+/+ 2d2 Th17 cells. Using two-photon laser scanning microscopy CCR7^-/- and CCR7^+/+ CD4⁺ T cells did not reveal differences in motility in either animal model of MS. These findings indicate a crucial role of CCR7 in neuroinflammation during the priming of autoimmune CD4⁺ T cells but not in the CNS.