Anti-Interferon-γ Autoantibodies Impair T-Lymphocyte Responses in Patients with Infections.

BACKGROUND

Although anti-IFN-γ autoantibodies predispose patients to infection, whether this is mediated by T cell attenuation remains elusive.

METHODS

Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with infection were stimulated with M1, and immunodominant influenza H1N1 peptide, or heat-inactivated in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γTNFCD8 T cells and IFN-γCD4 T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot.

RESULTS

The M1-reactive CD8 T cells that expressed IFN-γ TNF-α of healthy controls were clearly reduced in serum with high-titer anti-IFN-γ autoantibodies. In addition, the CD4 T cell response, designated by the expression of IFN-γ, against in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation.

CONCLUSION

Anti-IFN-γ autoantibodies presence in the serum inhibited CD4 Th1 and CD8 T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.