Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients.
Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients.
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DOI：
10.1126/scitranslmed.3003008
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发表时间：
2012-01-18
影响因子：
17.1
通讯作者：
Kupper TS
中科院分区：
文献类型：
--
作者：
Clark RA;Watanabe R;Teague JE;Schlapbach C;Tawa MC;Adams N;Dorosario AA;Chaney KS;Cutler CS;Leboeuf NR;Carter JB;Fisher DC;Kupper TS
CTCL是皮肤归巢T细胞的癌症，其变体包括白血病CTCL（L-CTCL）（中央记忆T细胞（TCM）的恶性肿瘤）和蕈样肉芽肿（MF）（皮肤驻留效应记忆T细胞（TEM）的恶性肿瘤）。我们报告低剂量Alemtuzumab（α CD 52）有效治疗难治性L-CTCL患者，但不能治疗MF。阿仑单抗耗尽血液中的所有T细胞，并耗尽皮肤中的良性和恶性TCM，但治疗后皮肤中仍保留有多种皮肤驻留TEM。Alemtuzumab的T细胞耗竭需要中性粒细胞的存在，这是一种在血液中常见但在正常皮肤中罕见的细胞类型。这些数据表明，TCM被耗尽，因为它们在血液和皮肤之间再循环，而皮肤驻留TEM被幸免，因为它们是固着的和非再循环的。在Alemtuzumab治疗后，皮肤T细胞产生较低量的IL-4和较高量的IFNγ。此外，尽管血液中完全不存在T细胞，但Alemtuzumab治疗的L-CTCL患者中明显缺乏感染，这表明即使在不存在T细胞从循环中募集的情况下，皮肤驻留TEM也可以保护皮肤免受病原体的侵害。总之，这些数据表明，Alemtuzumab可治疗难治性L-CTCL，而不会通过消耗循环TCM而严重损害对感染的免疫应答，但保留了提供皮肤局部免疫保护的皮肤驻留TEM。
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 skin whereas skin resident TEM were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of IL-4 and higher amounts of IFNγ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in 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.
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影响因子：
20.3
作者：
Dummer, R;Heald, PW;Burg, G
通讯作者：
Burg, G
DOI：
10.1084/jem.171.3.801
发表时间：
1990-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mackay CR;Marston WL;Dudler L
通讯作者：
Dudler L
影响因子：
20.3
作者：
Clark, Rachael A.;Shackelton, Jeffrey B.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
20.3
作者：
Lundin, J;Hagberg, H;Österborg, A
通讯作者：
Österborg, A
影响因子：
--
作者：
Kim, YH;Liu, HL;Hoppe, RT
通讯作者：
Hoppe, RT