CCR7 on CD4+ T Cells Plays a Crucial Role in the Induction of Experimental Autoimmune Encephalomyelitis.
J Immunol
; 200(8): 2554-2562, 2018 04 15.
Article
in En
| MEDLINE
| ID: mdl-29549177
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
Encephalomyelitis, Autoimmune, Experimental
/
Receptors, CCR7
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2018
Document type:
Article
Affiliation country: