Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma
Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma
复制标题
DOI：
10.1182/blood-2005-03-1139
复制
发表时间：
2006-03-15
期刊：
影响因子：
20.3
通讯作者：
Kupper, TS
中科院分区：
文献类型：
--
作者：
Yamanaka, K;Clark, R;Kupper, TS
皮肤T细胞淋巴瘤（CTCLS）是对皮肤具有特殊亲和力的T细胞的恶性肿瘤。我们以前曾报道，大部分的T细胞受体库改变CTCL，恶性和非恶性克隆的数量扩大，大概是在响应T细胞营养细胞因子。因此，我们检测了93名CTCL患者和健康对照者血浆中T细胞营养细胞因子IL-2、IL-4、IL-7、IL-12、IL-13和IL-15的水平。CTCL中仅IL-7水平升高。我们接下来观察了CTCL患者的病变皮肤，发现IL-7 mRNA水平升高。正常和病变CTCL皮肤活检组织的外植体培养物显示CTCL皮肤中显著更多的IL-7蛋白产生。此外，CTCL皮肤的培养物比正常皮肤释放更多数量的T细胞;这被添加IL-7中和抗体阻断。最后，这些培养物诱导加入培养物中的正常外周皮肤归巢T细胞增殖。这些观察结果使我们假设皮肤细胞产生的IL-7有助于皮肤病变内T细胞的存活和增殖，并且可能是CTCL中循环IL-7升高的来源。
Cutaneous T-cell lymphomas (CTCLS) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL.