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Artificial Antigen Presenting Cell aAPC Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate
Helen Y Lorenzo-Anota1, Alan B Martínez-Loria1, Reyes S Tamez-Guerra2
1Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Mexico; Unité de Biologie Cellulaire des Lymphocytes, Institut Pasteur, Paris, France.
Abstract:
Natural killer (NK) cells are CD3-, CD16+, CD56+ that play a crucial role in immune response by recognizing and eliminating a variety of virus-infected, malignant, and antibody-coated target cells. We examined activation; repertoire changes and effector functions of human NK cells normal donors treated with IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE) containing a mixture of low molecular weight molecules. I-CRP induces human NK cells activation and increase CD56Dim CD16- subset, without inducing proliferation. Human NK cells showed an increase on NKp30, NKp44, NKp46, NKG2D, NKG2C and KIR receptors, whereas no significant differences on CD160, CD85j and CD226 where observed. I-CRP-treated human NK cells exhibited an increased degranulation activity against K562 target cells, as shown by CD107a assay, and this correlates with cytotoxicity against K562 cells observed in calcein release assay. These results indicate that I-CRP can modify human NK cells receptor repertoire leading to an increased cytotoxic activity, supporting evidence for its use to stimulate NK cells.
Insights
IMMUNEPOTENT-CRP (I-CRP), a bovine extract, enhances natural killer (NK) cell activity. This extract modifies NK cell receptors, boosting their ability to eliminate target cells without causing proliferation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial immune cells that target virus-infected, malignant, and antibody-coated cells.
- NK cells are characterized as CD3-, CD16+, CD56+.
Purpose of the Study:
- To investigate the effects of IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE), on human NK cell activation, receptor repertoire, and effector functions.
- To determine if I-CRP influences NK cell proliferation.
Main Methods:
- Human NK cells from normal donors were treated with I-CRP.
- Flow cytometry was used to analyze changes in NK cell surface receptors (NKp30, NKp44, NKp46, NKG2D, NKG2C, KIR, CD160, CD85j, CD226) and subsets (CD56Dim CD16-).
- Degranulation activity was assessed using the CD107a assay, and cytotoxicity was measured via calcein release assay against K562 target cells.
Main Results:
- I-CRP treatment activated human NK cells and increased the CD56Dim CD16- subset, without inducing proliferation.
- Significant increases were observed in NK cell receptors NKp30, NKp44, NKp46, NKG2D, NKG2C, and KIR.
- I-CRP-treated NK cells showed enhanced degranulation and increased cytotoxicity against K562 cells.
Conclusions:
- I-CRP modifies the human NK cell receptor repertoire.
- This modification leads to enhanced NK cell cytotoxic activity.
- I-CRP demonstrates potential as an agent to stimulate NK cells.
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