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Modulation of natural killer (nk) cell activity during FLV-P virus infection of mice
Abstract:
We analyzed the effects of a polycythemic substrain of Friend leukemia virus, i.e. the FLV-P virus, on splenic NK activity of DBA/2 susceptible mice. One day after virus injection a significant increase of NK activity was found, which persisted until day 10. On the other hand, 14-21 days after virus injection a marked and significant depression of activity was measured. This depression was associated with the appearance of suppressor cells able to inhibit the lytic activity of untreated splenocytes when mixed in vitro in the 4 h 51Cr-release assay. The suppressor cell population was insensitive to treatment with anti-Thy 1.2 plus complement, was adherent to Sephadex G-10 and nylon, but did not adhere to plastic, suggesting it is neither a T-cell nor a typical macrophage. The possible relevance of NK activity modulation in relation to the induction of leukemia is discussed.
Insights
Friend leukemia virus (FLV-P) initially boosts splenic NK cell activity in mice, but later causes significant depression. Suppressor cells emerge, inhibiting NK cell function and potentially contributing to leukemia development.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Friend leukemia virus (FLV-P) is a polycythemic viral strain.
- Natural Killer (NK) cells play a role in anti-viral and anti-tumor immunity.
- DBA/2 mice are susceptible to FLV-P infection.
Purpose of the Study:
- To investigate the impact of FLV-P on splenic NK cell activity in DBA/2 mice.
- To characterize the cellular mechanisms underlying NK cell activity modulation during FLV-P infection.
Main Methods:
- Mice were infected with FLV-P.
- Splenic NK activity was measured using the 51Cr-release assay at various time points post-infection.
- Suppressor cell activity was assessed by in vitro co-culture assays.
- Cell surface markers and adherence properties were used to characterize suppressor cells.
Main Results:
- FLV-P infection led to a transient increase in NK activity by day 10 post-infection.
- A significant depression of NK activity was observed between 14-21 days post-infection.
- Suppressor cells, resistant to anti-Thy 1.2 treatment and adherent to Sephadex G-10 and nylon, were identified during the late phase of infection.
- These suppressor cells inhibited the lytic activity of normal splenocytes.
Conclusions:
- FLV-P infection induces a biphasic modulation of splenic NK cell activity.
- The late-stage depression of NK activity is mediated by non-T, non-macrophage suppressor cells.
- NK cell activity modulation may be relevant to the pathogenesis of FLV-P-induced leukemia.