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Published on: April 19, 2017
Modification of lymphocyte and monocyte functional activity by polymorphonuclear neutrophils in HIV infection
D I Gabrilovich1, G K Shepeleva, L V Serebrovskaya
1Laboratory of AIDS Epidemiology and Prevention, Central Institute for Epidemiology, Moscow, Russia.
Abstract:
The aim of this study was to determine whether polymorphonuclear neutrophils (PMN) can modify the immune response in HIV cases. Supernatants of PMN (PMNS) from 33 HIV-infected patients (16 with lymphoadenopathy syndrome, 17 with AIDS-related complex) were tested for their influence on the functional activity of lymphocytes and monocytes from 6 healthy donors. PMNS from another 6 healthy donors comprised a control group. It was found that PMNS from HIV-infected patients, but not from healthy donors, induced suppression of lymphocyte proliferative response and down-regulation of CD8 receptor expression on lymphocytes. Decrease of NK-cell cytotoxicity in the presence of PMNS from HIV-infected patients was the same as that from healthy donors. PMNS did not influence the production of anti-HIV antibody by lymphocytes from HIV-infected patients, as well as non-specific IgG by lymphocytes from healthy donors. PMNS effect on functional activity of lymphocytes was blocked completely after treatment of PMN by catalase and superoxide dismutase. At the same time PMNS from HIV-infected patients but not from healthy donors induced increased production of TNF-alpha by monocytes and up-regulation of monocyte phagocytosis. These effects were independent of catalase and superoxide dismutase and were not abrogated by antibody against IL-1, IL-8, TNF-alpha, IFN-gamma or IFN-alpha.
Insights
Polymorphonuclear neutrophils (PMN) from HIV patients suppress lymphocyte function and down-regulate CD8 expression. However, PMN from HIV patients also enhance monocyte TNF-alpha production and phagocytosis, indicating a complex immune modulation role.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- HIV infection significantly impacts the immune system, affecting various immune cells.
- Polymorphonuclear neutrophils (PMN) play a role in innate and adaptive immunity.
- The specific influence of PMN on immune responses in HIV-infected individuals requires further elucidation.
Purpose of the Study:
- To investigate the effect of PMN supernatants (PMNS) from HIV-infected patients on lymphocyte and monocyte function.
- To determine if PMNS from HIV patients differentially affect immune cells compared to healthy donors.
Main Methods:
- Supernatants from PMN of HIV patients and healthy donors were collected.
- The influence of these supernatants on lymphocyte proliferation, CD8 expression, NK-cell cytotoxicity, and antibody production was assessed.
- Monocyte function, including TNF-alpha production and phagocytosis, was also evaluated.
- The role of reactive oxygen species (ROS) and cytokines was investigated using specific inhibitors and antibodies.
Main Results:
- PMNS from HIV patients suppressed lymphocyte proliferation and down-regulated CD8 receptor expression.
- NK-cell cytotoxicity and antibody production (anti-HIV and IgG) were not significantly affected by PMNS.
- PMNS from HIV patients increased monocyte TNF-alpha production and phagocytosis, effects independent of ROS and major cytokines.
- The suppressive effects on lymphocytes were abrogated by catalase and superoxide dismutase treatment.
Conclusions:
- PMN from HIV-infected individuals exert a dual effect on the immune system, suppressing lymphocyte activity while enhancing certain monocyte functions.
- The observed effects on lymphocytes are mediated by ROS, while monocyte activation appears independent of ROS and common cytokines.
- These findings highlight the complex and potentially detrimental role of PMN in HIV pathogenesis.
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