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Cyclophosphamide-induced suppressor cells in nude mice
M Shimizu1, D Sabolovic, H Ozawa
1Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Anti-Cancer Drugs
|August 1, 1992
Summary
High-dose cyclophosphamide (CY) treatment in mice regenerates natural suppressor cells. These cells, characterized by increased electrophoretic mobility (EPM) and histamine receptors, suppress antibody production while maintaining natural killer (NK) activity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Cyclophosphamide (CY) is an immunosuppressive drug used in chemotherapy.
- Understanding the regeneration of immune cells post-CY treatment is crucial for managing side effects and developing therapeutic strategies.
Purpose of the Study:
- To characterize lymphocytes that regenerate after high-dose cyclophosphamide (CY) treatment in nude mice.
- To identify the properties and functions of these regenerated suppressor cells.
Main Methods:
- Nude mice were administered a single high dose of CY (200 mg/kg).
- Spleen cells were analyzed 10 days post-treatment for antibody production, natural killer (NK) activity, B and T cell content, cell surface charge (electrophoretic mobility - EPM), and histamine receptors.
- Suppressor cell activity was assessed by testing the effect of cell depletion using anti-Thy-1 plus complement (C) and antiasialo GM1 (aGM1) plus C.
Main Results:
- Regenerated spleen cells from CY-treated mice suppressed in vitro antibody production.
- These cells exhibited normal natural killer (NK) activity but had very low B and T cell content.
- Increased cell surface charge (electrophoretic mobility - EPM) and histamine receptors were observed on CY-treated spleen cells.
- Depletion of NK cells using anti-Thy-1 plus C or antiasialo GM1 plus C did not remove the suppressor cells.
Conclusions:
- The regenerated suppressor cells following CY treatment are characterized by high electrophoretic mobility (EPM) and histamine receptors.
- These cells are identified as natural suppressor cells, lacking Ig, Thy-1, and aGM-1 markers.