Brain tumor T cells inhibited by their natural KLR(B1) instinct

2021 ◽  
Vol 6 (58) ◽  
pp. eabi7302
Author(s):  
Seneca Oxendine ◽  
Kevin C. O’Connor
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Brain Tumor ◽  
Nk Cell ◽  
Glioma Cells ◽  
Cell Receptors ◽  
Nk Cell Receptors

Charting the gene-expression landscape of glioma-infiltrating T cells demonstrates that these T cells can express NK cell receptors, which inhibit the killing of glioma cells.

scholarly journals OTME-8. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Simon Gritsch ◽  
Nathan Mathewson ◽  
Orr Ashenberg ◽  
Elizabeth Perez ◽  
Sascha Marx ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Receptors ◽  
Human Cancers ◽  
Nk Cell Receptors ◽  
Diffuse Gliomas

Abstract T-cells are critical effector cells of cancer immunotherapies, but little is known about T-cell gene expression programs in diffuse gliomas. We leveraged single-cell RNA-seq to chart the gene expression and clonal landscape of tumor-infiltrating T-cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. Our analysis revealed subsets of T-cells that expressed several NK-cell receptors, in particular the inhibitory CD161 receptor (KLRB1 gene). KLRB1 was overexpressed by clonally expanded CD8 T-cells, and larger populations of T-cells expressed CD161 than PD-1. The CLEC2D ligand of CD161 was expressed by malignant cells and myeloid cells, and inactivation of KLRB1 enhanced anti-tumor T-cell function. KLRB1 was also expressed by substantial T-cell populations in multiple other human cancers. CD161 and other NK-cell receptors expressed by T-cells represent opportunities for immunotherapy of diffuse gliomas and other human cancers.

Expression and function of NK cell receptors in CD8+ T cells

2001 ◽  
Vol 13 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Christopher W McMahon ◽  
David H Raulet
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors ◽  
And Function

scholarly journals Differential Requirements for IRF-2 in Generation of CD1d-Independent T Cells Bearing NK Cell Receptors

2012 ◽  
Vol 188 (10) ◽  
pp. 4838-4845 ◽  
Author(s):  
Tsuyoshi Notake ◽  
Shin Horisawa ◽  
Hideki Sanjo ◽  
Shin-ichi Miyagawa ◽  
Shigeaki Hida ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors

scholarly journals Emergence of CD8+T Cells Expressing NK Cell Receptors in Influenza A Virus-Infected Mice

2000 ◽  
Vol 165 (9) ◽  
pp. 4964-4969 ◽  
Author(s):  
Taku Kambayashi ◽  
Erika Assarsson ◽  
Jakob Michaëlsson ◽  
Peter Berglund ◽  
Alexander D. Diehl ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza A Virus ◽  
Cd8 T Cells ◽  
Influenza A ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors

Activating NK-cell receptors co-stimulate CD4+CD28−T cells in patients with rheumatoid arthritis

2010 ◽  
Vol 40 (2) ◽  
pp. 378-387 ◽  
Author(s):  
Andreas E. R. Fasth ◽  
Niklas K. Björkström ◽  
Minna Anthoni ◽  
Karl-Johan Malmberg ◽  
Vivianne Malmström
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors

scholarly journals Viral and Bacterial Infections Induce Expression of Multiple NK Cell Receptors in Responding CD8+ T Cells

2002 ◽  
Vol 169 (3) ◽  
pp. 1444-1452 ◽  
Author(s):  
Christopher W. McMahon ◽  
Allan J. Zajac ◽  
Amanda M. Jamieson ◽  
Laura Corral ◽  
Gianna E. Hammer ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Bacterial Infections ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors

T Cells Expressing the Activating NK Cell Receptors KIR2DS4, NKG2C and NKG2D Are Elevated In Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) and Cytotoxic towards Hematopoietic Progenitor Cell Lines

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2235-2235
Author(s):  
Sandra van Bijnen ◽  
Marian Withaar ◽  
Frank Preijers ◽  
Arnold van der Meer ◽  
Theo de Witte ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Nk Cell ◽  
Cytolytic Activity ◽  
Hematopoietic Progenitor Cell ◽  
Effector Memory ◽  
Cell Receptors ◽  
Nk Cell Receptors ◽  
Hematopoietic Cell Lines

Abstract Abstract 2235 Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease characterized by hemolysis due to an acquired mutation in the X-linked PIG-A gene in the hematopoietic stem cell (HSC). This leads to a clone of hematopoietic cells with deficient expression of glycosyl phosphatidyl inositol (GPI) anchored proteins at the cell membrane. The clinical evolution of PNH arises through clonal expansion of PIG-A mutated HSC which is insufficiently explained by the PIG-A mutation alone. Hypothetically, clonal expansion could result from autoreactive T cells selectively attacking normal HSC, whereas GPI deficient HSC are unharmed. Methods and Results: we investigated the presence of potentially autoreactive T cells in peripheral blood of patients with PNH (n = 39) by flow cytometry. We compared T cell subset frequencies and absolute numbers with healthy controls (n = 25) using Mann-Whitney U test. In PNH patients, T cells expressing the NK cell marker CD56 were significantly elevated, both in percentage (p < 0.001) and in absolute numbers (p < 0.01). Furthermore, the frequency of T cells expressing the activating NK cell receptors (NKRs) NKG2D (p < 0.01), NKG2C (p < 0.01), and KIR2DS4 (p = 0.01) was significantly increased. KIR2DS4+, NKG2C+ and NKG2D+ T cells mainly consist of highly differentiated effector memory CD45RA+ T cells (TEMRA) (KIR2DS4: median 90%, range 70–96%, NKG2C: median 83%, range 49–99%, NKG2D: median 40%, range 38–66%). A highly variable proportion of these T cell populations consists of γδ T cells (KIR2DS4: median 28%, range 6–72%, NKG2C: median 36%, range 3–75%, NKG2D: median 11%, range 7–40%). By 10 color flow cytometry, we examined NKR coexpression patterns. KIR2DS4+ and NKG2C+ T cells mainly coexpress either only NKG2D (KIR2DS4+ T cells: median 24%, range 2 – 74%, NKG2C+ T cells: median 21%, range 3–71%), or a combination of NKG2D, NKG2C and CD158b1/b2,j, but not inhibitory NKG2A (KIR2DS4+ T cells: median 16%, range 1 – 55%, NKG2C+ T cells: median 20%, range 1–60%). In contrast, NKG2D+ T cells generally do not express any other NKRs tested (median 77%, range 53–84%). NKG2D+ KIR2DS4+ cytotoxic T lymphocyte (CTL) lines isolated from PNH patient peripheral blood and bone marrow display high cytolytic activity towards CD34+ hematopoietic progenitor cell lines and MHC class I deficient K562 cells, suggesting T cell receptor independent cytolytic activity. These NKR+ CTL lines are capable of differentially lysing GPI+ and GPI- hematopoietic cell lines, however not in all cell line models and CTL lines. This suggests that multiple factors, as for example the highly activated status of in vitro cultured CTLs, influence whether or not GPI dependent lysis occurs. Conclusion: The increased frequency of T cells expressing activating NK cell receptors KIR2DS4, NKG2C, and NKG2D, with a CD8+ effector-memory phenotype and differences in cytotoxicity towards GPI+ and GPI- hematopoietic cell lines suggests that these T cell populations may be involved in bone marrow failure and expansion of PNH clones. Disclosures: Muus: Alexion: member of advisory board.

Opposing functions of activatory T-cell receptors and inhibitory NK-cell receptors on cytotoxic T cells

1996 ◽  
Vol 17 (10) ◽  
pp. 450-453 ◽  
Author(s):  
Ermanno Ciccone ◽  
Carlo Enrico Grossi ◽  
Andrea Velardi
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Nk Cell ◽  
Cytotoxic T Cells ◽  
Cell Receptors ◽  
Nk Cell Receptors
Sign in / Sign up

Export Citation Format

Share Document