一项新的发表于Sci Transl Med杂志上的研究"Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients"可帮助解释为什么一种叫做阿仑单抗的药物对治疗罹患某种叫做皮肤T细胞淋巴瘤或CTCL的瘙痒加疼痛类型的皮肤癌非常有效。
此外，阿仑单抗的治疗似乎不会增加感染的风险——这是一个意外的发现，因为该药会杀灭所有的T和B免疫细胞，而这些细胞都是至关重要的抗感染斗士。 传统的观念预计，接受阿仑单抗治疗的病人会比感染了HIV的患者的病情更重—HIV也会消灭T细胞--但这些病人并没有病情变得更重。
Rachael Clark及其同事对几位CTCL病人进行观察之后发现了其究竟。 研究人员给病人低剂量的阿仑单抗并观察到这些患者的病情好转且没有随之出现感染。 接着，该小组分析了采自那些已完全康复病人的皮肤样本并注意到其皮肤中的T细胞执行着监控感染的职责。
与在血液中循环的T细胞不同——这些T细胞会游走到出现问题的部位以保护身体不受侵犯，研究人员发现了非移动性的皮肤T细胞——这是一组新发现的固守在某个社区，在此为皮肤，中的等待麻烦出现的警员。
原来，阿仑单抗只杀灭循环中的T细胞，但它不会打扰那些处在皮肤组织中的T细胞。 由于在这种疾病中的恶性T细胞是在血液中循环游走的，因此该药可在清除这种疾病的同时让组织中的免疫记忆保持大体上的完整，因而防止更多的感染发生。 （生物谷Bioon.com）
doi: 10.1126/scitranslmed.3003008
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Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients
Rachael A. Clark1,2,*, Rei Watanabe1,*, Jessica E. Teague1, Christoph Schlapbach1, Marianne C. Tawa2, Natalie Adams2, Andrew A. Dorosario2, Keri S. Chaney1, Corey S. Cutler2, Nicole R. LeBoeuf1, Joi B. Carter3, David C. Fisher2 and Thomas S. Kupper1,2,*
Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (TCM), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (TEM). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant TCM from skin, but a diverse population of skin resident TEM remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that TCM were depleted because they recirculate between the blood and the skin, whereas skin resident TEM were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident TEM can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating TCM but sparing the skin resident TEM that provide local immune protection of the skin.
