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CXCR3 blockade inhibits T‐cell migration into the CNS during EAE and prevents development of adoptively transferred, but not actively induced, disease

Sporici, Romeo ; Issekutz, Thomas B.

European journal of immunology, 2010-10, Vol.40 (10), p.2751-2761 [Periódico revisado por pares]

Weinheim: WILEY‐VCH Verlag

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Título:
CXCR3 blockade inhibits T‐cell migration into the CNS during EAE and prevents development of adoptively transferred, but not actively induced, disease
Autor: Sporici, Romeo ; Issekutz, Thomas B.
Assuntos: Adoptive Transfer - methods ; Animals ; Antibodies, Monoclonal - pharmacology ; Autoimmunity ; Cell adhesion & migration ; Cell Movement - immunology ; Central Nervous System - immunology ; Chemokines ; Encephalomyelitis, Autoimmune, Experimental - immunology ; Encephalomyelitis, Autoimmune, Experimental - therapy ; Flow Cytometry ; Histocytochemistry ; Inflammation ; Interferon-gamma - genetics ; Interferon-gamma - immunology ; Interleukin-17 - genetics ; Interleukin-17 - immunology ; Rats ; Rats, Inbred Lew ; Receptors, CXCR3 - administration & dosage ; Receptors, CXCR3 - antagonists & inhibitors ; Receptors, CXCR3 - immunology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - chemistry ; RNA, Messenger - genetics ; Rodents ; T cells ; T-Lymphocytes - immunology
É parte de: European journal of immunology, 2010-10, Vol.40 (10), p.2751-2761
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Autoreactive T‐cell infiltration into the CNS is critical in MS and EAE. The chemokine receptor CXCR3 and its ligands are implicated in MS and mouse EAE, but the contribution of CXCR3 to T‐cell migration into the inflamed CNS remains controversial. During active disease in a rat EAE model, blood T‐cell, spleen T‐cell and T lymphoblast migration into the CNS was inhibited by a CXCR3 blocking mAb by, 30–70%, ∼75% and 50–80%, respectively. However, CXCR3 blockade after active immunization did not inhibit EAE, did not alter total T‐cell accumulation in the CNS and did not affect Treg accumulation or the presence of cells producing IFN‐γ or IL‐17. Conversely, CXCR3 blockade during EAE induced by adoptive transfer of myelin basic protein‐activated T cells delayed disease onset, shortened its duration and reduced disease severity. Moreover, CXCR3 blockade inhibited leukocyte infiltration of the CNS>95%, virtually abolishing infiltration of transferred T cells. Thus, CXCR3 plays a major role in T‐cell migration to the CNS and can be critical for encephalitogenic T‐cell migration into the CNS to induce disease, but CXCR3‐independent recruitment can also produce EAE.
Editor: Weinheim: WILEY‐VCH Verlag
Idioma: Inglês

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CXCR3 blockade inhibits T‐cell migration into the CNS during EAE and prevents development of adoptively transferred, but not actively induced, disease

Sporici, Romeo ; Issekutz, Thomas B.

Weinheim: WILEY‐VCH Verlag

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