CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats.
J Immunol
; 197(11): 4274-4282, 2016 12 01.
Article
em En
| MEDLINE
| ID: mdl-27799310
ABSTRACT
Discovery of immune tolerance mechanisms, which inhibit pre-existing autoimmune inflammation, may provide us with new strategies for treating autoimmune diseases. We have identified a CD8αα+MHC class II+ cell with professional APC capacity during our investigation on spontaneous recovery from autoimmune glomerulonephritis in a rat model. This cell actively invades inflamed target tissue and further terminates an ongoing autoimmune inflammation by selective killing of effector autoreactive T cells. In this study, we show that this cell used a cytotoxic machinery of Ly49s+ NK cells in killing of target T cells. Thus, this CD8αα+MHC class II+ cell was a dually functional Ag-presenting NK-like (AP-NK) cell. Following its coupling with target T cells through Ag presentation, killing stimulatory receptor Ly49s6 and coreceptor CD8αα on this cell used rat nonclassic MHC class I C/E16 on the target T cells as a ligand to initiate killing. Thus, activated effector T cells with elevated expression of rat nonclassic MHC class I C/E16 were highly susceptible to the killing by the CD8αα+ AP-NK cell. Granule cytolytic perforin/granzyme C from this cell subsequently mediated cytotoxicity. Thus, inhibition of granzyme C effectively attenuated the killing. As it can recognize and eliminate effector autoreactive T cells in the inflamed target tissue, the CD8αα+ AP-NK cell not only represents a new type of immune cell involved in immune tolerance, but it also is a potential candidate for developing a cell-based therapy for pre-existing autoimmune diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Células Matadoras Naturais
/
Antígenos de Histocompatibilidade Classe II
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Antígenos CD8
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Glomerulonefrite
/
Células Apresentadoras de Antígenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article