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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Membrane interactions involved in the induction of acid labile interferon alpha
M R Capobianchi1, F Malavasi, P Mattana
1Institute of Virology, University of Roma, Italy.
Insights
Human peripheral blood mononuclear cells produce acid-labile interferon-alpha (IFN-α) when stimulated. B lymphocytes are key, with HLA Class II and CD4 antigens crucial for this IFN-α induction process.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human peripheral blood mononuclear cells (PBMC) generate acid-labile interferon-alpha (IFN-α) upon stimulation with HIV-infected cells.
- B lymphocytes are identified as the primary producers of this specific IFN-α subtype.
Purpose of the Study:
- To pinpoint the precise cellular origins of acid-labile IFN-α.
- To investigate the membrane interactions critical for its induction.
Main Methods:
- PBMC stimulation with acid-labile IFN-α inducers.
- Utilizing monoclonal antibodies against lymphocyte membrane antigens (HLA Class I, II, CD4).
- Comparing PBMC and B cell line responses.
Main Results:
- Both HLA Class II and CD4 antigens are integral to the induction of acid-labile IFN-α.
- B cell lines can produce conventional IFN-α but not the acid-labile form, even with CD4+ T cell cooperation.
- PBMC lose the capacity for acid-labile IFN-α production after 20 hours of culture.
Conclusions:
- The induction of acid-labile IFN-α by PBMC is dependent on specific membrane interactions involving HLA Class II and CD4.
- The loss of acid-labile IFN-α production in cultured PBMC may be due to altered membrane structures or early functional changes in B cells.
Abstract:
Human normal peripheral blood mononuclear cells (PBMC) produce acid-labile interferon (IFN) alpha when stimulated in vitro with HIV-infected cells fixed with glutaraldehyde. The cells responsible for IFN production are mainly B lymphocytes. The present study was aimed to further elucidate the cellular source of this IFN and to analyze the membrane interactions involved in the induction process. To this purpose PBMC were stimulated with inducers of acid labile IFN alpha in the presence or absence of a panel of monoclonal antibodies (MoAbs) against antigens of the lymphocyte membrane, namely HLA Class I and II and CD4. The results indicate that both HLA Class II and CD4 antigens are involved in the induction process. Conversely B cell lines seem capable of producing conventional alpha IFN but they fail to produce acid labile IFN alpha even in the presence of cooperating CD4 positive T cell lines. Furthermore PBMC cultured for more than 20 hours prior to stimulation lose the ability to produce acid labile IFN alpha, while remaining fully capable of producing conventional IFN alpha and gamma. It remains to be established whether this phenomenon reflects the disappearance of some membrane structure necessary for acid labile IFN alpha induction, or whether it is due to some early appearing functional alteration of B cells.
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