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Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455
Stimulation of an effective in vitro or in vivo response by naive
CD8 T cells requires three signals: TCR engagement, costimulation/IL-2,
and a third signal that can be provided by IL-12. In addition to being
required for acquisition of cytolytic function, IL-12 is required for
optimal IL-2-dependent proliferation and clonal expansion. In
experiments examining in vitro stimulation of naive CD8 T cells, IL-12
is shown to stimulate expression of the IL-2R 
-chain (CD25) to much
higher levels than are reached in response to just TCR and
costimulation and/or IL-2. In addition, high CD25 expression is
substantially prolonged in the presence of IL-12. As a consequence, the
cells proliferate more effectively in response to low levels of IL-2.
Examination of adoptively transferred TCR transgenic CD8 T cells
responding to peptide Ag confirmed that IL-12 up-regulates CD25 in
vivo, even when B7-mediated costimulation is largely blocked. TCR- and
IL-2-dependent proliferation of CD8 T cells from mice deficient in CD25
was also found to increase in the presence of IL-12, indicating that
CD25 up-regulation is not the only mechanism by which IL-12 increases
clonal expansion of the cells. IL-2 and IL-12 both act to increase
expression of both CD25 and the IL-12R, thus providing positive
cross-regulation of receptor expression. These results suggest that
when cross-priming dendritic cells present class I/Ag and costimulatory
ligands, and produce IL-12, naive CD8 T cells will begin to produce
IL-2 and both receptors will be optimally up-regulated to insure that
an effective response is generated.
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