Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells

Dendritic cells (DC) are critically involved in the initiation of primary i mmune processes, including tumor rejection. In our study, we investigated t he effect of interleukin-10 (IL-10)-treated human DC on the properties of C D8(+) T cells that are known to be essential for the destruction of tumor c ells. We show that IL-10-pretreatment of DC not only reduces their allostim ulatory capacity, hut also induces a state of alloantigen-specific anergy i n both primed and naive (CD45RA(+)) CD8(+) T cells. To investigate the infl uence 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 D C, restimulation of the T-cell line with untreated, antigen-pulsed DC demon strated peptide-specific anergy in the tyrosinase-specific T cells. Additio n 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 cell s, 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-treate d DC induce an antigen-specific anergy in cytotoxic CD8(+) T cells, a proce ss that might be a mechanism of tumors to inhibit immune surveillance by co nverting DC into tolerogenic antigen-presenting cells. (C) 1999 by The Amer ican Society of Hematology.