CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats

• Published in: The Journal of immunology (1950) 2016-12, Vol.197 (11), p.4274-4282
• Main Authors: Wu, Jean, Carlock, Colin, Ross, April, Shim, Junbo, Lou, Yahuan
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - pathology; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; CD8 Antigens - immunology; Female; Glomerulonephritis - immunology; Glomerulonephritis - pathology; Granzymes - immunology; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; Inflammation - immunology; Inflammation - pathology; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Rats; Rats, Inbred Lew; Rats, Inbred WKY
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601207

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.