Priming in the Presence of IL-10 Results in Direct Enhancement of CD8+ T Cell Primary Responses and Inhibition of Secondary Responses

Abstract

Although IL-10 acts as an inhibitory cytokine for APC and CD4+ T cell function, its effects on CD8+ T cells are unclear. Additionally, little is known about whether initial priming in the presence of IL-10 can have long-lasting effects and influence subsequent CD8+ T cell responses that occur in the absence of the cytokine. In the present study, we clarified the role of IL-10 during primary responses and examined whether exposure to IL-10 during initial priming of CD8+ T cells impacted secondary responses. To determine the effect of IL-10 on Ag-specific T cell responses, peptide-pulsed IL-10R2−/− splenic dendritic cells were used to prime T cells from OT-I CD8+ TCR transgenic mice. During the primary response, the presence of IL-10 resulted in enhancement of CD8+ T cell numbers without detectable alterations in the kinetics or percentage of cells that underwent proliferation. A modest increase in survival, not attributable to Bcl-2 or Bcl-xL, was also observed with IL-10 treatment. Other parameters of CD8+ T cell function, including IL-2, IFN-γ, TNF-α, and granzyme production, were unaltered. In contrast, initial exposure to IL-10 during the primary response resulted in decreased OT-I expansion during secondary stimulation. This was accompanied by lowered IL-2 levels and reduced percentages of proliferating BrdU+ cells and OT-I cells that were CD25high. IFN-γ, TNF-α, and granzyme production were unaltered. These data suggest that initial exposure of CD8+ T cells to IL-10 may be temporarily stimulatory; however, programming of the cells may be altered, resulting in diminished overall responses.