Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8+ T cells resulting in a failure to lyse tumor cells
Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8+ T cells resulting in a failure to lyse tumor cells
复制标题
DOI：
10.1182/blood.v93.5.1634.405k11_1634_1642
复制
发表时间：
1999-03-01
期刊：
影响因子：
20.3
通讯作者：
Enk, AH
中科院分区：
文献类型：
--
作者：
Steinbrink, K;Jonuleit, H;Enk, AH
树突状细胞（DC）在原发性免疫过程的启动中起着关键作用，包括肿瘤排斥反应。在我们的研究中，我们研究了白细胞介素-10 （IL-10）处理的人DC对CD8(+) T细胞特性的影响，CD8(+) T细胞是破坏肿瘤细胞所必需的。我们发现il -10预处理DC不仅降低了它们的同种异体刺激能力，而且还诱导了启动和初始（CD45RA(+)） CD8(+) T细胞的同种异体抗原特异性能量状态。为了研究il -10处理DC对黑色素瘤相关抗原特异性T细胞的影响，我们通过几轮特异性抗原刺激产生了酪氨酸酶特异性CD8(+) T细胞系。在与il -10处理的DC共培养后，用未处理的抗原脉冲DC再刺激T细胞系，在酪氨酸酶特异性T细胞中显示出肽特异性能量。向失能T细胞中添加IL-2可逆转同种抗原或肽特异性能的状态。与最佳刺激的CD8(+) T细胞相比，无能酪氨酸酶特异性CD8(+) T细胞在与肽脉冲il -10处理的DC共培养后，无法裂解hla - a2阳性和酪氨酸酶表达的黑色素瘤细胞系。因此，我们的数据表明，il -10处理的DC在细胞毒性CD8(+) T细胞中诱导抗原特异性能量，这一过程可能是肿瘤通过将DC转化为耐受性抗原呈递细胞来抑制免疫监视的机制。(C) 1999年由美国血液病学会出版。
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, hut 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. (C) 1999 by The American Society of Hematology.