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Enhancement of cytotoxicity of human peripheral blood lymphocytes by interferon
Abstract:
Human lung carcinoma cells persistently infected with mumps virus (Pc-10/MpV) were lysed with human peripheral blood mononuclear leukocytes (PBML) obtained from seropositive donors who had anti-mumps virus-neutralizing antibody in their sera. This cellular cytotoxicity was due not to the cytotoxic T lymphocytes but mainly to the non-T, non-B cells, possibly related to natural killer (NK) cells. Moreover, it was concerned not with antibody against mumps virus antigens but with alpha-interferon (IFN-alpha) produced in the mixture of human PBML and Pc-10/MpV cells, since this cellular cytotoxicity was suppressed by anti-human IFN-alpha rabbit serum. Exogeneous IFN-alpha augmented the cytotoxicity of non-T, non-B cells, not T cells, for the uninfected Pc-10 cells. IFN-gamma that had been induced by heat-killed Listeria monocytogenes in PBML had the same capacity to augment NK activity did IFN-alpha.
Insights
Human peripheral blood mononuclear leukocytes (PBML) exhibit cytotoxicity against mumps virus-infected lung carcinoma cells. This effect is mediated by non-T, non-B cells, likely natural killer (NK) cells, and enhanced by alpha-interferon (IFN-alpha).
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human lung carcinoma cells persistently infected with mumps virus (Pc-10/MpV) were studied.
- Peripheral blood mononuclear leukocytes (PBML) from donors with anti-mumps virus antibodies were used.
Purpose of the Study:
- To investigate the mechanism of cellular cytotoxicity against mumps virus-infected lung carcinoma cells.
- To determine the role of different immune cells and cytokines in this cytotoxic response.
Main Methods:
- Co-culture of Pc-10/MpV cells with human PBML.
- Assessment of cytotoxicity using non-T, non-B cells and T lymphocytes.
- Evaluation of the role of alpha-interferon (IFN-alpha) and its suppression by anti-human IFN-alpha rabbit serum.
- Investigation of exogenous IFN-alpha and IFN-gamma effects on cell cytotoxicity.
Main Results:
- Cytotoxicity was mainly mediated by non-T, non-B cells, possibly natural killer (NK) cells, not cytotoxic T lymphocytes.
- The cytotoxicity was linked to alpha-interferon (IFN-alpha) production, not anti-mumps virus antibodies.
- Anti-human IFN-alpha serum suppressed the observed cellular cytotoxicity.
- Exogenous IFN-alpha augmented the cytotoxicity of non-T, non-B cells against uninfected cells.
- IFN-gamma also augmented NK activity similarly to IFN-alpha.
Conclusions:
- Natural killer (NK) cell-mediated cytotoxicity plays a significant role in eliminating mumps virus-infected lung carcinoma cells.
- Alpha-interferon (IFN-alpha) is a key mediator of this NK cell activity.
- Both endogenous and exogenous IFN-alpha, as well as IFN-gamma, can enhance NK cell-mediated cytotoxicity against tumor cells.