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CCR7 on CD4(+) T cells plays a crucial role in the induction of experimental autoimmune encephalomyelitis

Item Type:Article
Title:CCR7 on CD4(+) T cells plays a crucial role in the induction of experimental autoimmune encephalomyelitis
Creators Name:Belikan, P., Bühler, U., Wolf, C., Pramanik, G.K., Gollan, R., Zipp, F. and Siffrin, V.
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.
Keywords:Animal Disease Models, CCR7 Receptors, CD4-Positive T-Lymphocytes, Central Nervous System, Experimental Autoimmune Encephalomyelitis, Inbred C57BL Mice, Lymph Nodes, Multiple Sclerosis, T-Cell Antigen Receptors, Th17 Cells, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:2554-2562
Date:15 April 2018
Official Publication:https://doi.org/10.4049/jimmunol.1701419
PubMed:View item in PubMed

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