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-Producing T Cells from Tumor-Infiltrating Lymphocytes1
*
Department of Dermatology, School of Medicine, University of Würzburg, Würzburg, Germany; and
Department of Tumor Cell Biology, Danish Cancer Society, Copenhagen, Denmark
Professional APC, notably dendritic cells (DC), are necessary for
stimulation and expansion of naive T cells. By means of murine models,
the interaction between CD40 on DC and its ligand CD154 has been
recognized as an important element for conditioning of DC to prime and
expand CTL. We translated these findings into the human system,
scrutinizing the ability of DC to initiate clonal expansion of single T
cells. DC generated under completely autologous conditions from
peripheral blood monocytes were cocultured at a rate of 0.3 cell/well
with melanoma-infiltrating T cells; this procedure guaranteed that
either a CD4+ or a CD8+ cell interacted with
the DC, thus avoiding the contact of more than one T cell to the DC. In
the absence of further stimulation, this cloning protocol yielded
almost exclusively CD4+ T cell clones that predominantly
exhibited a Th2 phenotype. However, cross-linking of CD40 on DC
resulted in the induction of IFN-
-producing Th1 CD4+ T
cell clones. In addition, CD40-activated DC were capable of expanding
CD8+ CTL clones. The ratio of CD4 to CD8 T cell clones
corresponded to the ratio present in the initial tumor-infiltrating
lymphocyte preparation. The CTL clones efficiently lysed autologous
tumor cells whereas autologous fibroblasts or MHC-mismatched melanoma
cells were not killed. Our findings support the critical role of
CD40/CD154 interactions for the induction of cellular immune
responses.
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