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Natural cytotoxic cells against solid tumors in mice: blocking of cytotoxicity by D-mannose
Abstract:
Natural cytotoxic (NC) and natural killer (NK) cells have been defined by their ability to lyse certain solid or lymphoid tumor targets in vitro, without prior sensitization. Our present studies describe an attempt to characterize the structures involved in the effector-target recognition leading to tumor cell lysis. Addition of the monosaccharide D-mannose to the NC cell assay significantly blocked cytotoxicity of the fibrosarcoma Meth A target by the effector cells at 50 mM and lower concentrations. D-Galactose showed blocking activity in one of five experiments, only at 50 mM. L-Fucose, D-glucose, and N-acetyl-D-glucosamine did not affect NC cell cytotoxicity at similar concentrations. All of the sugars tested inhibited NK cell lysis of the lymphoma YAC-I target. None of the sugars affected killing of the appropriate target by allosensitized cytotoxic T lymphocytes. The blocking of NC-mediated cytotoxicity was not due to a direct toxic action of the sugars on the effector cells. These findings suggest that, in the NC system, recognition involves lectin-like structures with a specificity for D-mannose (or D-galactose, or both), whereas, in the NK system, such lectin-like structures are less restricted. Such structures appear not to be involved in the specific cytotoxicity mediated by T cells.
Insights
Natural cytotoxic (NC) and natural killer (NK) cells utilize lectin-like structures for target recognition. D-mannose specifically blocks NC cell cytotoxicity, while various sugars inhibit NK cell activity against tumor cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural cytotoxic (NC) and natural killer (NK) cells are innate immune cells capable of lysing tumor cells without prior sensitization.
- Understanding the molecular mechanisms of effector-target recognition is crucial for elucidating innate immune responses.
Purpose of the Study:
- To characterize the specific structures involved in effector-target recognition during tumor cell lysis mediated by NC and NK cells.
- To investigate the role of carbohydrate-binding lectins in NC and NK cell-mediated cytotoxicity.
Main Methods:
- In vitro cytotoxicity assays using fibrosarcoma (Meth A) and lymphoma (YAC-I) target cells.
- Inhibition studies involving the addition of various monosaccharides (D-mannose, D-galactose, L-fucose, D-glucose, N-acetyl-D-glucosamine) to effector cell assays.
- Comparison with allosensitized cytotoxic T lymphocyte (CTL) activity.
Main Results:
- D-mannose significantly blocked NC cell cytotoxicity against Meth A cells at concentrations of 50 mM and lower.
- D-galactose showed weak blocking activity in one experiment.
- All tested sugars inhibited NK cell lysis of YAC-I cells, indicating broader lectin-like specificities.
- No tested sugars affected CTL-mediated cytotoxicity, suggesting distinct recognition mechanisms.
Conclusions:
- NC cell recognition of tumor targets involves lectin-like structures with specificity for D-mannose (and possibly D-galactose).
- NK cell recognition exhibits less restricted lectin-like specificities compared to NC cells.
- These lectin-like structures are not involved in the specific cytotoxicity mediated by T cells.