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Published on: June 22, 2016
Suppressive effect of kanglemycin C on T- and B-lymphocyte activation
Insights
Kanglemycin C (Kan) suppresses T- and B-lymphocyte proliferation, impacting T-cell subsets. This immunosuppressive effect is time-dependent and not due to toxicity, offering a selective alternative to ciclosporin.
Area of Science:
- Immunology
- Pharmacology
Background:
- Lymphocyte proliferation is crucial for immune responses.
- Understanding novel immunosuppressants is vital for therapeutic development.
Purpose of the Study:
- To investigate the immunosuppressive effects of kanglemycin C (Kan) on lymphocyte proliferation.
- To analyze the impact of Kan on T-lymphocyte subsets.
Main Methods:
- Splenocyte proliferation assessed using [3H]thymidine ([3H]TdR) and MTT assays.
- T-cell subsets (L3T4+ and Lyt2+) quantified via fluorescence-activated cell sorting (FACS).
- Splenocyte viability confirmed with trypan blue exclusion.
Main Results:
- Kanglemycin C inhibited lymphocyte proliferation stimulated by various mitogens and alloantigens, similar to ciclosporin.
- Kan demonstrated no toxicity to splenocytes at tested concentrations.
- Kan selectively altered the L3T4+/Lyt2+ T-cell ratio, unlike ciclosporin.
Conclusions:
- Kan exhibits immunosuppressive activity against T- and B-lymphocytes.
- Kan selectively affects the helper-inducer T-lymphocyte subset.
- The suppressive action of Kan is time-dependent and non-toxic.
Aim:
To elucidate the suppressive effect of kanglemycin C (Kan) on lymphocyte proliferation and T-lymphocyte subsets.
Methods:
Splenocyte proliferation was quantified with [3H]thymidine ([3H]TdR) pulsing method or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetery. L3T4+ and Lyt2+ T-cell subsets were measured with fluorescence-activated cell sorter (FACS). Splenocyte viability was assessed with trypan blue exclusion.
Results:
Like ciclosporin (Cic), Kan 8, 40, 80, and 400 nmol.L-1 inhibited the proliferation of 20%-80% incubated mouse splenocytes stimulated by concanavalin A (Con A) 5 mg.L-1, phytohemagglutinin (PHA) 5 mg.L-1, tetradecanoylphorbol acetate (TPA) 10 micrograms.L-1 + ionomycin (IM) 0.5 mg.L-1, and alloantigen (mixed lymphocyte reaction). Kan had no toxicity to the splenocytes at the treated doses. Suppression by Kan was declined with addition time of Kan after culture onset. Furthermore, the suppressive effect of Kan on splenocyte proliferation stimulated by lipopolysaccharides (LPS) 10 mg.L-1 was similar to that on splenocyte proliferation mediated by Con A. Unlike Cic, Kan reversed the ratio of L3T4+/Lyt2+ T-cell subsets.
Conclusion:
Kan had a suppressive action on proliferation of T- and B-lymphocytes and had a selective effect on helper-inducer T-lymphocyte (Th) subset from Cic. Suppression by Kan was time-dependent and not associated with toxicity of Kan.
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