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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1634-1642
Interleukin-10-Treated Human Dendritic Cells Induce a
Melanoma-Antigen-Specific Anergy in CD8+ T Cells
Resulting in a Failure to Lyse Tumor Cells
Kerstin Steinbrink,
Helmut Jonuleit,
Gabriele Müller,
Gerold Schuler,
Jürgen Knop, and
Alexander H. Enk
From the Department of Dermatology, University of Mainz, Mainz,
Germany; and the Department of Dermatology, University of Erlangen,
Erlangen, Germany.
Dendritic cells (DC) are critically involved in the initiation of
primary immune processes, including tumor rejection. In our study, we
investigated the effect of interleukin-10 (IL-10)-treated human DC on
the properties of CD8+ T cells that are known to be
essential for the destruction of tumor cells. We show that
IL-10-pretreatment of DC not only reduces their allostimulatory
capacity, but also induces a state of alloantigen-specific anergy in
both primed and naive (CD45RA+) CD8+ T
cells. To investigate the influence of IL-10-treated DC on melanoma-associated antigen-specific T cells, we generated a
tyrosinase-specific CD8+ T-cell line by several rounds of
stimulation with the specific antigen. After coculture with
IL-10-treated DC, restimulation of the T-cell line with untreated,
antigen-pulsed DC demonstrated peptide-specific anergy in the
tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells
reversed the state of both alloantigen- or peptide-specific anergy. In
contrast to optimally stimulated CD8+ T cells, anergic
tyrosinase-specific CD8+ T cells, after coculture with
peptide-pulsed IL-10-treated DC, failed to lyse an HLA-A2-positive
and tyrosinase-expressing melanoma cell line. Thus, our data
demonstrate that IL-10-treated DC induce an antigen-specific anergy in
cytotoxic CD8+ T cells, a process that might be a
mechanism of tumors to inhibit immune surveillance by converting DC
into tolerogenic antigen-presenting cells.
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