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Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
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-
,
TNF-
, 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-, TNF-, 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.
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