Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity.

نویسندگان

  • Athanasia E Christakou
  • Mathias Ohlin
  • Bruno Vanherberghen
  • Mohammad Ali Khorshidi
  • Nadir Kadri
  • Thomas Frisk
  • Martin Wiklund
  • Björn Önfelt
چکیده

Natural killer (NK) cells kill virus-infected or cancer cells through the release of cytotoxic granules into a tight intercellular contact. NK cell populations comprise individual cells with varying sensitivity to distinct input signals, leading to disparate responses. To resolve this NK cell heterogeneity, we have designed a novel assay based on ultrasound-assisted cell-cell aggregation in a multiwell chip allowing high-resolution time-lapse imaging of one hundred NK-target cell interactions in parallel. Studying human NK cells' ability to kill MHC class I deficient tumor cells, we show that approximately two thirds of the NK cells display cytotoxicity, with some NK cells being particularly active, killing up to six target cells during the assay. We also report that simultaneous interaction with several susceptible target cells increases the cytotoxic responsiveness of NK cells, which could be coupled to a previously unknown regulatory mechanism with implications for NK-mediated tumor elimination.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Characterization of Natural Killer Cells’ Cytotoxic Heterogeneity Using an Array of Sono-cages

Using a multi-well device as an array of sono-cages for single cell analysis, we quantify for the first time the heterogeneity of natural killer (NK) cells’ cytotoxic response against cancer cells. We report a fraction of inactive NK cells within the tested population (36%), as well as the existence of few ‘serial killers’ that eliminate up to six targets during 4 hours. We also characterize th...

متن کامل

Killer Cell Immunoglobulin-Like Receptors Influence the Innate and Adaptive Immune Responses

Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibi...

متن کامل

Natural Killer Cell Cytotoxicity Against SKOV3 after HLA-G Downregulation by shRNA

Background: HLA-G is a nonclassical HLA class I molecule which, when elevated in tumor cells, is one of the main factors involved in tumor evasion of immune responses including NK and T cells. Objective: To evaluate the effect of HLA-G downregulation on NK cell cytotoxicity in tumor cell lines. Methods: The expression level of HLA-G was measured by real-time PCR and flowcytometry after transfec...

متن کامل

The Efficacy of Toll-Like Receptors in Awakening Dendritic Cell/Natural Killer Cell System for Eradication of Tumors

Natural killer (NK) cells are effector cells of the innate immune system that exert direct cytotoxic functions. Ubiquitously-expressed toll-like receptors (TLRs) have been recognized as one of the major components promoting dendritic cell (DC) maturation, which may induce polarized immune responses beneficial to cancer immunotherapy. TLR-activated NK cells and DCs are prerequisite for robust ac...

متن کامل

Increased Natural Killer Cells Activity in Schizophrenic Patients

Background: Schizophrenia has been associated with altered immunity. Different studies regarding natural killer cell activity (NKA) in schizophrenic patients have shown inconsistent results. Objectives: To evaluate NK cell activity in schizophrenic patients in comparison with healthy control individuals.   Methods: 30 medication-free schizophrenic patients and 41 healthy sex, age and smoking st...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Integrative biology : quantitative biosciences from nano to macro

دوره 5 4  شماره 

صفحات  -

تاریخ انتشار 2013