Distinct effects of two different human interferon-alpha subtypes on indicators of T-cell proliferation, activation and inhibition.

Humans produce 12 distinct interferon alpha (IFN-α) subtypes that were previously thought to be functionally redundant. Recent studies have revealed that IFN-α subtypes differ in their ability to control different viral infections. However, little is known about how IFN-α subtypes differentially modulate immune cells to mediate these effects. This study compared the effects of IFN-α2 and IFN-α14, subtypes identified to differentially control viral infection, on T cells both in vivo in humanized TKO-BLT mice and in vitro using human peripheral blood mononuclear cells (PBMC). Treatment of humanized mice with the 2 IFN-α subtypes resulted in the differential modulation of genes associated with T-cell immunity, such as proliferation, activation and inhibition. Therefore, we assessed whether stimulation of PBMC in the presence of IFN-α2 or IFN-α14 resulted in subtype-specific effects on T cells in vitro. IFN-α14 decreased the proliferation of human CD4+ and CD8+ T cells significantly more than IFN-α2. Additionally, IFN-α14 increased expression of T-cell activation markers and the frequency of IL-2 producing T cells to a significantly greater extent compared to IFN-α2. However, the co-culture of CD8+ T cells with IFN-α-treated, autologous CD4+ T cells or IFN-α-matured monocyte-derived dendritic cells (mo-DC) only increased the expression of CD38 compared to no IFN-α treatment in a non-subtype specific manner. Overall, we identified IFN-α subtype-specific effects on the proliferation and activation of T cells. However, there were no significant differences detected directly between the IFN-α subtypes when the effects on CD8+ T cells arose through IFN-α pre-treatment of CD4+ T cells or mo-DC.