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Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455
Challenge with peptide Ag in the absence of adjuvant results in
tolerance of CD8 T cells specific for the Ag. In contrast,
administration of IL-12 along with peptide results in massive clonal
expansion, development of effector function, and establishment of a
long-lived memory population. Using adoptive transfer of TCR-transgenic
CD8 T cells, this effect of IL-12 is shown to be independent of CD4 T
cells and to require costimulation provided by CD28 and possibly LFA-1.
IL-12 supports responses when IL-12R
1-deficient mice are used as
recipients for the adoptively transferred CD8 T cells, demonstrating
that the IL-12 is acting directly on the T cells rather than on host
APC. These results provide strong support for a three-signal model for
in vivo activation of naive CD8 T cells by peptide Ag, in which the
presence or absence of the third signal determines whether tolerance or
activation occurs. In contrast, memory CD8 T cells are effectively
activated by peptide Ag in the absence of IL-12 or
adjuvant.
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