Inhibitory receptors that recognize MHC class I molecules regulate NK cell responses and self-tolerance. Recent evidence indicates that self-ligands not present in the MHC locus also can modulate NK function. In this study, we show that an inhibitory receptor that recognizes an MHC-independent ligand is over expressed in SHIP(-/-) mice at all stages of NK development and differentiation. Overexpression of this receptor compromises key cytolytic NK functions, including killing of allogeneic, tumor, and viral targets. These results further demonstrate the critical role that SHIP plays in regulation of the NK receptor repertoire and show that regulation of MHC-independent inhibitory receptors is crucial for NK recognition and cytolysis of complex targets.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4049/jimmunol.176.12.7165 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hypoimmunogenic CD19 CAR-NK cells derived from embryonic stem cells suppress the progression of human B-cell malignancies in xenograft animals.
Front Immunol
December 2024
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Background: Chimeric antigen receptor (CAR) engineered natural killer (NK) cells exhibit advantages such as MHC-independent recognition and strong anti-tumor functions. However, allogeneic CAR-NK cells derived from human tissues are heterogeneous and susceptible to clearance by hosts.
Methods: We generated a B2M knockout, HLA-E and CD19 CAR ectopic expressing embryonic stem cell (ESC) line, which differentiated normally and gave rise to homogeneous CD19 CAR-NK (CD19 CAR-UiNK) cells using an organoid aggregate induction method.
γδ T cells and the PD-1/PD-L1 axis: a love-hate relationship in the tumor microenvironment.
J Transl Med
June 2024
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Gamma delta (γδ) T cells demonstrate strong cytotoxicity against diverse cancer cell types in an MHC-independent manner, rendering them promising contenders for cancer therapy. Although amplification and adoptive transfer of γδ T cells are being evaluated in the clinic, their therapeutic efficacy remains unsatisfactory, primarily due to the influence of the immunosuppressive tumor microenvironment (TME). Currently, the utilization of targeted therapeutic antibodies against inhibitory immune checkpoint (ICP) molecules is a viable approach to counteract the immunosuppressive consequences of the TME.
View Article and Find Full Text PDFSiglec-9 defines and restrains a natural killer subpopulation highly cytotoxic to HIV-infected cells.
PLoS Pathog
November 2021
The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Siglec-9 is an MHC-independent inhibitory receptor expressed on a subset of natural killer (NK) cells. Siglec-9 restrains NK cytotoxicity by binding to sialoglycans (sialic acid-containing glycans) on target cells. Despite the importance of Siglec-9 interactions in tumor immune evasion, their role as an immune evasion mechanism during HIV infection has not been investigated.
View Article and Find Full Text PDFCanonical Wnts Mediate CD8 T Cell Noncytolytic Anti-HIV-1 Activity and Correlate with HIV-1 Clinical Status.
J Immunol
October 2020
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612;
CD8 T cells do not rely solely on cytotoxic functions for significant HIV control. Moreover, the noncytotoxic CD8 T cell antiviral response is a primary mediator of natural HIV control such as that seen in HIV elite controllers and long-term nonprogressors that does not require combined antiretroviral therapy. In this study, we investigated the biological factors contributing to the noncytotoxic control of HIV replication mediated by primary human CD8 T cells.
View Article and Find Full Text PDFCombination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model.
J Immunother Cancer
August 2020
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background: T cells have been recognized as core effectors for cancer immunotherapy. How to restore the anti-tumor ability of suppressed T cells or improve the lethality of cytotoxic T cells has become the main focus in immunotherapy. Bispecific antibodies, especially bispecific T cell engagers (TCEs), have shown their unique ability to enhance the patient's immune response to tumors by stimulating T cell activation and cytokine production in an MHC-independent manner.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!