McCarter Martin, Clarke Jason, Richter Donald, Wilson Cara
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Surgery. 2005 Aug;138(2):321-8. doi: 10.1016/j.surg.2005.06.011.
Patients with progressing melanoma have a circulating cytokine profile reflecting a T helper cell type 2 (Th2) imbalance, while patients responding to therapy favor a Th1 profile. The aim of this study was to determine the role of circulating dendritic cells (DCs) in mediating this imbalance.
Isolated human peripheral blood mononuclear cells (PBMCs) were exposed to cell-free melanoma-conditioned medium (MCM) or control fibroblast-conditioned medium before stimulation. In separate experiments, isolated circulating DCs were exposed to MCM before addition of T cells. DC maturation and function were determined. Mixed leukocyte response T-cell proliferation was quantified and supernatants were assayed for Th1 (interleukin [IL]-2 and interferon gamma) and Th2 (IL-4, IL-5, and IL-10) cytokines.
PBMCs exposed to MCM produced significantly more Th2-type cytokines (IL-4, IL-5, and IL-10) over time than those exposed to control medium. DCs exposed to MCM before addition of T cells, produced a similar pattern of a sustained longer term Th2 response after an initial burst of IL-2. Exposure to MCM did not significantly affect DC maturation or IL-12 production. T-cell proliferation did not change significantly in the mixed leukocyte response, however, the percentage of viable CD4+ T cells in the MCM-treated group was significantly less than control (37 vs 50%, P < .05).
Exposure of PBMCs to melanoma produces a Th2-type cytokine profile, which may be, in part, facilitated by DCs.
进展期黑色素瘤患者的循环细胞因子谱反映了辅助性T细胞2型（Th2）失衡，而对治疗有反应的患者则倾向于Th1谱。本研究的目的是确定循环树突状细胞（DC）在介导这种失衡中的作用。
分离的人外周血单个核细胞（PBMC）在刺激前暴露于无细胞黑色素瘤条件培养基（MCM）或对照成纤维细胞条件培养基。在单独的实验中，分离的循环DC在加入T细胞之前暴露于MCM。测定DC的成熟和功能。对混合淋巴细胞反应T细胞增殖进行定量，并检测上清液中的Th1（白细胞介素[IL]-2和干扰素γ）和Th2（IL-4、IL-5和IL-10）细胞因子。
随着时间的推移，暴露于MCM的PBMC比暴露于对照培养基的PBMC产生显著更多的Th2型细胞因子（IL-4、IL-5和IL-10）。在加入T细胞之前暴露于MCM的DC，在最初的IL-2爆发后产生了类似的持续较长时间的Th2反应模式。暴露于MCM对DC成熟或IL-12产生没有显著影响。在混合淋巴细胞反应中T细胞增殖没有显著变化，然而，MCM处理组中存活CD4+T细胞的百分比显著低于对照组（37%对50%，P<.05）。
PBMC暴露于黑色素瘤会产生Th2型细胞因子谱，这可能部分由DC促成。
