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Natural killer-cell-mediated and antibody-dependent cellular cytotoxicity in leprosy
S V Chiplunkar1, M V Deshmukh, P D Samson
1Cancer Research Institute, Tata Memorial Centre, Bombay, India.
Insights
Leprosy patients exhibit reduced natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC). However, these immune functions in lepromatous leprosy patients can be improved with lymphokine treatments like IL-2 and IFN-alpha.
Area of Science:
- Immunology
- Cellular Biology
- Infectious Diseases
Background:
- Leprosy, a chronic infectious disease, significantly impacts the immune system.
- Natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC) are crucial for immune defense.
- Understanding immune cell function in leprosy patients is vital for developing effective treatments.
Purpose of the Study:
- To evaluate NK cell-mediated cytotoxicity and ADCC in leprosy patients.
- To assess the impact of multidrug therapy (MDT) on these immune functions.
- To investigate the potential of lymphokines (IL-2, IFN-alpha) to enhance immune responses in leprosy.
Main Methods:
- Peripheral blood lymphocytes (PBL) were analyzed from untreated lepromatous leprosy (LL), multidrug therapy (MDT)-treated LL (MDT-R, MDT-NR), treated tuberculoid leprosy (TT) patients, and healthy donors.
- NK cytotoxicity and ADCC were measured.
- PBL were treated with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) to assess modulation of NK activity.
Main Results:
- Untreated LL patients and MDT-treated LL patients showed significantly lower NK cytotoxicity compared to TT patients and healthy donors.
- ADCC activity was reduced in untreated LL patients but normal in TT patients.
- IL-2 and IFN-alpha enhanced NK cytotoxicity in most LL and some TT patients, indicating lymphokine responsiveness.
Conclusions:
- Lepromatous leprosy is associated with impaired NK cell and ADCC functions.
- While MDT improves some immune parameters, LL patients exhibit persistent deficits in cytotoxicity.
- Lymphokine therapy holds promise for restoring NK cell activity in leprosy patients.
Abstract:
We have assessed the natural killer (NK) cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) in the peripheral blood lymphocytes (PBL) from untreated lepromatous leprosy (LL) patients, LL patients on multidrug therapy (MDT) with favorable responses (MDT-R), LL patients clinically classified as nonresponders to MDT (MDT-NR), treated tuberculoid leprosy (TT) patients, and healthy donors. NK cytotoxicity was modulated by treating the PBL with recombinant interferon-alpha (IFN-alpha) and recombinant interleukin-2 (IL-2). The mean percent NK cytotoxicity of untreated LL patients (15 +/- 3), treated MDT-R patients (20 +/- 4), and treated MDT-NR patients (12 +/- 4) was significantly lower than that of TT patients (39 +/- 6) and healthy donors (37 +/- 5). Treatment of effectors with IL-2 or IFN-alpha enhanced NK cytotoxicity in 5 of 6 untreated LL patients, 6 of 6 treated MDT-R LL patients, 4 of 5 and 3 of 5 treated MDT-NR LL patients, respectively, and 5 of 8 and 3 of 8 treated TT patients, respectively. Although PBL from TT patients showed initial NK activity comparable to that of healthy donors, fewer TT patients showed modulation of NK activity by IL-2, and IFN-alpha to a lesser extent. The ADCC activity was lower in untreated LL patients compared to treated patients, while TT patients had normal ADCC activity. The results indicate that although LL patients show lowered spontaneous cytotoxicity, it can be modulated favorably by lymphokines.
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