Intravenous immunoglobulin therapy affects T regulatory cells by increasing their suppressive function

Intravenous Ig therapy (IVIg) is reported to be a useful regimen in treating autoimmune diseases. In this study, we asked whether IVIg (in vitro) could increase the expression of TGF-beta, IL-10, and the transcription factor FoxP3 in T regulatory (Treg) cells, and the idea that IVIg could enhance suppressive properties of these cells. CD4(+) T cells from 12 healthy individuals were cultured in the presence or absence of IVIg vs human control IgG during 16,24, and 36 h. Using FACS analysis and gating on CD4(+)CD25(high) Treg cells, we assessed the expression of intracellular TGF-beta, IL-10, and FoxP3. In addition, the production of TNF-alpha by stimulated CD4(+) T cells alone or in culture with CD25(+) by itself or together with IVIg was also assessed. The presence of IVIg with Treg cells in culture significantly increased the intracellular expression of TGF-beta (17.7 +/- 8.5% vs 29.8 +/- 13%; p = 0.02), IL-10 (20.7 +/- 4.7% vs 34.2 +/- 5.2%; p = 0.008) and FoxP3 (20.8 +/- 5.2% vs 33.7 +/- 5.9%; p = 0.0006) when compared with cells cultured alone or with control human IgG. The suppressive effect of CD4(+)CD25(+) T cells presented as the decrease of TNF-alpha production by stimulated CD4(+)CD25(-) (effector T cells) was further increased by adding IVIg to cell culture. We hereby demonstrate an additional mechanism by which IVIg could maintain self-tolerance and decrease immune-mediated inflammation.