title: CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats.
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.
authors: Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77054.
authors: Jean
authors: J
authors: Wu
authors: Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77054.
authors: Colin
authors: C
authors: Carlock
authors: Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77054.
authors: April
authors: A
authors: Ross
authors: Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77054.
authors: Junbo
authors: 0000-0002-4219-5526
authors: J
authors: Shim
authors: Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77054 Yahuan.lou@uth.tmc.edu.
authors: Yahuan
authors: Y
authors: Lou
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D053804:Granzymes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053804:Granzymes; C509217:Gzmc protein, rat