Harwix S, Zachmann K, Neumann C
Department of Dermatology, Göttingen University, von-Siebold-Str. 3, 37075 Göttingen, Germany.
Arch Dermatol Res. 2000 Jan;292(1):1-8. doi: 10.1007/pl00007454.
Recent studies of the cytokine pattern in skin lesions of patients with cutaneous T-cell lymphoma (CTCL) have shown that interleukin-4 (IL-4) and Il-10, both cytokines produced by T-helper type 2 cells, dominate in these lesions. Also, in single studies, interferon-gamma (IFN-gamma), a major cytokine of Th-1-cells, has been found to be absent. Consequently, it has been hypothesized that immune-suppressive Th-2 cytokines may promote local growth of the malignant lymphocyte clone. However, there is so far no evidence for T-cells as the source of the Th-2 cytokines in CTCL skin lesions nor have these cytokines been investigated at a clonal T-cell level. We established a total of 120 T-cell clones (TCCs) from lesional skin and 54 TCCs from the blood of four patients with mycosis fungoides. Epidermal TCCs (mostly CD8-positive) and dermal TCCs (mostly CD4-positive) were stimulated by the mitogen concanavalin A and, seeking a polarized cytokine pattern, the supernatants were assessed by ELISA. We showed that the vast majority of TCCs were able to secrete IFN-gamma and IL-4. IFN-gamma-deficient TCCs occurred only in the epidermis. Some (18) TCCs were found to be either negative for IL-10 production or to produce low levels only. No significant differences were observed between blood- and skin-derived TCCs. Thus a polarized Th-2 cytokine pattern was not detectable among cultured skin-infiltrating nonmalignant T-cells (TILs) isolated from early mycosis fungoides. It therefore appears unlikely that Th-2-mediated immune suppression is a major mechanism operating in early CTCL. However, this does not exclude its role in late-stage disease.
近期对皮肤T细胞淋巴瘤（CTCL）患者皮肤病变中细胞因子模式的研究表明，白细胞介素-4（IL-4）和IL-10这两种由2型辅助性T细胞产生的细胞因子在这些病变中占主导地位。此外，在个别研究中，还发现缺乏1型辅助性T细胞的主要细胞因子干扰素-γ（IFN-γ）。因此，有人推测免疫抑制性的2型辅助性T细胞细胞因子可能促进恶性淋巴细胞克隆的局部生长。然而，到目前为止，尚无证据表明T细胞是CTCL皮肤病变中2型辅助性T细胞细胞因子的来源，也未在克隆性T细胞水平上对这些细胞因子进行研究。我们从4例蕈样肉芽肿患者的病变皮肤中总共建立了120个T细胞克隆（TCC），并从血液中建立了54个TCC。用促细胞分裂剂刀豆球蛋白A刺激表皮TCC（大多为CD8阳性）和真皮TCC（大多为CD4阳性），为了寻找极化的细胞因子模式，通过酶联免疫吸附测定法评估上清液。我们发现绝大多数TCC能够分泌IFN-γ和IL-4。仅在表皮中出现缺乏IFN-γ的TCC。发现一些（18个）TCC要么不产生IL-10，要么仅产生低水平的IL-10。在血液来源和皮肤来源的TCC之间未观察到显著差异。因此，在从早期蕈样肉芽肿中分离出的培养的皮肤浸润性非恶性T细胞（TIL）中未检测到极化的2型辅助性T细胞细胞因子模式。因此，2型辅助性T细胞介导的免疫抑制似乎不太可能是早期CTCL中的主要作用机制。然而，这并不排除其在晚期疾病中的作用。
