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Leukemia in AKR mice: a defined suppressor cell population expressing membrane-associated DNA
Summary
Leukemic mouse spleen cells suppress normal antibody responses. DNase I treatment removes this suppression, indicating cell-surface DNA is involved in immunosuppression and identifying a specific cell population responsible.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Leukemic AKR mouse spleen cells exhibit immunosuppressive properties.
- Normal antibody production is inhibited by these leukemic cells in vitro.
Purpose of the Study:
- To investigate the mechanism of immunosuppression by leukemic AKR mouse spleen cells.
- To identify the specific cellular components responsible for this suppressive effect.
Main Methods:
- Treatment of leukemic spleen cells with DNase I and observation of its effect on immunosuppression.
- Assessment of cell viability using [(3)H]thymidine incorporation and eosin dye exclusion.
- Investigation of DNase I activity by chelating divalent cations with EDTA.
- Utilizing anti-single-stranded-DNA and anti-immunoglobulin immunoadsorption chromatography to isolate specific cell populations.
Main Results:
- DNase I treatment abrogated the suppressive ability of leukemic spleen cells without affecting cell viability.
- EDTA abolished the DNase I effect, suggesting a requirement for divalent cations.
- Enriched cell populations, isolated using immunoadsorption, showed a 10-fold greater suppressive ability.
- DNase I's effect could not be mimicked by other enzymes like trypsin, Pronase, or ribonuclease.
Conclusions:
- A population of leukemic AKR mouse spleen cells expresses membrane-associated DNA responsible for immunosuppression.
- This cell-surface DNA plays a crucial role in the observed inhibition of normal antibody responses.
- Targeting this DNA may offer a novel therapeutic strategy for managing leukemia-associated immunosuppression.