Interferon-alpha regulation of lymphocyte function in systemic lupus erythematosus

Area of Science:

• Immunology
• Cellular Biology
• Autoimmune Diseases

Background:

• Interferon (IFN) production and responsiveness are often abnormal in systemic lupus erythematosus (SLE).
• Previous studies suggest a broad defect in IFN response in SLE patients.
• The specific cellular targets of IFN dysregulation in SLE require further elucidation.

Purpose of the Study:

• To investigate the abnormalities in interferon (IFN) response in patients with systemic lupus erythematosus (SLE).
• To determine if the impaired IFN response in SLE is specific to certain immune cells or a general lymphocyte defect.
• To explore the role of natural killer cytotoxic factor (NKCF) in the observed IFN response abnormalities.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from SLE patients and normal controls were used.
• Interferon-alpha (IFN-alpha) response was assessed using natural killer (NK) cell activity assays, T-cell proliferation assays (Concanavalin A), and B-cell blastogenesis systems (Pokeweed Mitogen).
• IFN-induced natural killer cytotoxic factor (NKCF) release was measured in SLE patients and controls.

Main Results:

• NK cell activity was significantly impaired in SLE patients compared to normal controls.
• The response to IFN-alpha in the NK cell system was markedly reduced in SLE patients.
• In contrast, the effect of IFN-alpha on T-cell and B-cell blastogenesis was normal in SLE patients, indicating a specific defect in NK cells.
• IFN-induced NKCF release was significantly impaired in SLE and correlated with the reduced IFN-induced NK cell enhancement.
• No depletion of NK cells was observed in SLE patients.

Conclusions:

• The study demonstrates that the impaired interferon (IFN) response in systemic lupus erythematosus (SLE) is not a universal lymphocyte defect.
• The defect appears to be isolated to the natural killer (NK) cell system, which is functionally abnormal in SLE.
• Impaired IFN-induced natural killer cytotoxic factor (NKCF) release contributes to the functional abnormality of NK cells in SLE.