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-x(L), was also observed with IL-10 treatment. Other parameters of CD8(+) T cell function, including IL-2, IFN-gamma, TNF-alpha, 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 CD25(high). IFN-gamma, TNF-alpha, 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.