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Human polymorphonuclear leucocytes as mediators of antibody-dependent cellular cytotoxicity to herpes simplex
Abstract:
Human polymorphonuclear leucocytes (PML) were able to mediate antibody-dependent cellular cytotoxicity (ADCC) against target cells acutely infected with type 1 Herpes simplex virus. The reaction mediated by PML occurred more slowly and required higher concentrations of immune serum than that mediated by human mononuclear cells (MC). At the same ratio of effector cells to target cells, PML-mediated ADCC was less than MC-mediated ADCC. The observed relationship between the number of effector cells added, and the number of target cells lysed, showed that cytolysis mediated by both PML and MC was consistent with 'one hit' probability predictions. This suggested that target cell death resulted from an interaction with a single effector cell. The calculated frequency of effector cells in PML preparation was similar to that in MC, approximately 3-5%. Preliminary examination of the nature of the effector cells suggested that they did not comprise a morphologically distinct subclass of PML. These experiments demonstrate a possible new role for PML in host defence against viral infections.
Insights
Human polymorphonuclear leucocytes (PML) can perform antibody-dependent cellular cytotoxicity (ADCC) against Herpes simplex virus-infected cells. This immune response is slower and less potent than that mediated by mononuclear cells (MC).
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Herpes simplex virus (HSV) infections pose a significant public health challenge.
- Antibody-dependent cellular cytotoxicity (ADCC) is a crucial immune mechanism for clearing viral infections.
- The role of polymorphonuclear leucocytes (PML) in ADCC against viral targets requires further elucidation.
Purpose of the Study:
- To investigate the capacity of human polymorphonuclear leucocytes (PML) to mediate antibody-dependent cellular cytotoxicity (ADCC) against Herpes simplex virus type 1 (HSV-1) infected cells.
- To compare the efficiency and kinetics of PML-mediated ADCC with that of human mononuclear cells (MC).
Main Methods:
- Human peripheral blood mononuclear cells (PBMC) and polymorphonuclear leucocytes (PML) were isolated.
- Target cells were acutely infected with HSV-1.
- Antibody-dependent cellular cytotoxicity (ADCC) assays were performed using varying effector to target cell ratios and immune serum concentrations.
- Cytolysis was quantified and analyzed using 'one hit' probability models.
Main Results:
- Human PML demonstrated the ability to mediate ADCC against HSV-1 infected target cells.
- PML-mediated ADCC was slower and required higher immune serum concentrations compared to MC-mediated ADCC.
- PML-mediated ADCC was less efficient than MC-mediated ADCC at equivalent effector cell ratios.
- The frequency of effective effector cells within PML preparations was comparable to that within MC preparations (3-5%).
- Effector cells within PML did not appear to be a morphologically distinct subclass.
Conclusions:
- Human PML can contribute to host defense against HSV-1 through ADCC.
- PML represent a potential, albeit less potent, effector cell population in antiviral immunity.
- These findings suggest a novel role for PML in combating viral infections, complementing the activity of mononuclear cells.