Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin.
Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin.
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人肠道 Vdelta1+ 淋巴细胞识别上皮来源的肿瘤细胞。
DOI：
10.1084/jem.183.4.1681
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发表时间：
1996-04-01
影响因子：
15.3
通讯作者：
Lotze, MT
中科院分区：
文献类型：
--
作者：
Maeurer, MJ;Martin, D;Walter, W;Liu, KH;Zitvogel, L;Halusczcak, K;Rabinowich, H;Duquesnoy, R;Storkus, W;Lotze, MT
根据 T 细胞受体 (TCR) 可变 (V) 区家族的表达、组织分布及其特异性，γδ T 细胞可分为离散的亚群。 Vdelta2+ T 细胞构成外周血中 γδ T 细胞的大部分，而 Vdelta1+ T 细胞优先存在于皮肤上皮和肠道中。 γδ T 细胞被设想为一线宿主防御机制，能够提供免疫效应 T 细胞和免疫调节细胞因子（例如白细胞介素 (IL) 4 或干扰素 (IFN) γ）的来源。我们在这里描述了从原发性或转移性结直肠癌患者获得的三种不同的γδ+肿瘤浸润淋巴细胞（TIL）的精细特异性，这些细胞可以在IL-1β和IL-7存在的情况下在体外容易地扩增。无论供体如何，这些单独的 γδ T 细胞都表现出相似的反应模式，通过识别自体和同种异体结直肠癌细胞、肾细胞癌、胰腺癌和从人肠中新鲜分离的外植体来定义，通过溶细胞 T 细胞反应和 IFN-γ 释放来测量。相比之下，其他组织学的肿瘤没有被裂解，包括肺癌、鳞状细胞癌以及天然/淋巴细胞激活的杀伤细胞敏感的造血细胞系T2、C1R或Daudi。与结直肠癌靶标相比，K562 细胞系的裂解效果较差。 Vdelta1+ T 细胞介导的靶细胞反应被针对 TCR、β2 或 β7 整联蛋白链或纤连蛋白受体的抗体部分阻断。使用流式细胞术进行的标记分析表明，所有三种 γδ T 细胞系均表现出相似的表型。对 gammadelta TCR 连接的分析表明，仅使用具有广泛（< 或 = 29 bp）N/P 区域多样性的 Vdelta1/Ddelta3/Jdelta1 TCR 片段。 T细胞对靶细胞的识别似乎不是主要的组织相容性复合物限制的或与热休克蛋白的靶细胞表达相关的。基于一些上皮性肿瘤（包括结直肠癌、胰腺癌和肾细胞癌）有效冷靶抑制这些 Vdelta1+ T 细胞系对结直肠癌细胞系裂解的能力，我们建议肠道 Vdelta1+ T 细胞系，我们建议肠道 Vdelta1+ T 细胞能够识别上皮来源肿瘤共有的细胞表面 Ag。
gammadelta T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. Vdelta2+ T cells constitute the majority of gammadelta T cells in peripheral blood whereas Vdelta1+T cells reside preferentially in skin epithelium and in the intestine. gammadelta T cells are envisioned as first line host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) gamma. We describe here the fine specificity of three distinct gammadelta+ tumor-infiltrating lymphocytes (TIL) obtained from patients with primary or metastatic colorectal cancer, that could be readily expanded in vitro in the presence of IL-1beta and IL-7. Irrespective of donor, these individual gammadelta T cells exhibited a similar pattern of reactivity defined by recognition of autologous and allogeneic colorectal cancer cells, renal cell cancer, pancreatic cancer, and a freshly isolated explant from human intestine as measured by cytolytic T cell responses and by IFN-gamma release. In contrast, tumors of alternate histologies were not lysed, including lung cancer, squamous cell cancer, as well as the natural/lymphocyte-activated killer cell-sensitive hematopoietic cell lines T2, C1R, or Daudi. The cell line K562 was only poorly lysed when compared with colorectal cancer targets. Target cell reactivity mediated by Vdelta1+ T cells was partially blocked with Abs directed against the TCR, the beta2 or beta7 integrin chains, or fibronectin receptor. Marker analysis using flow cytometry revealed that all three gammadelta T cell lines exhibit a similar phenotype. Analysis of the gammadelta TCR junctional suggested exclusive usage of the Vdelta1/Ddelta3/Jdelta1 TCR segments with extensive (< or = 29 bp) N/P region diversity. T cell recognition of target cells did not appear to be a major histocompatibility complex restricted or to be correlated with target cell expression of heat- shock proteins. Based on the ability of some epithelial tumors, including colorectal, pancreatic, and renal cell cancers to effectively cold target inhibit the lysis of colorectal cancer cell lines by these Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cells are capable of recognizing cell surface Ag(s) shared by tumors of epithelial origin.
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DOI：
10.1084/jem.180.1.183
发表时间：
1994-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chowers Y;Holtmeier W;Harwood J;Morzycka-Wroblewska E;Kagnoff MF
通讯作者：
Kagnoff MF
影响因子：
5
作者：
Ferrick, D A;Gemmell-Hori, L;Mak, T W
通讯作者：
Mak, T W
鼠类上皮内淋巴细胞的免疫调节功能：γ/Delta T细胞受体阳性（TCR+）T细胞消除口服耐受性，而α/βTCR+ TCR+ TCR细胞可提供B细胞帮助。
影响因子：
15.3
作者：
FUJIHASHI, K;TAGUCHI, T;AICHER, WK;MCGHEE, JR;BLUESTONE, JA;ELDRIDGE, JH;KIYONO, H
通讯作者：
KIYONO, H
影响因子：
64.8
作者：
FERRICK, DA;SCHRENZEL, MD;LEPPER, H
通讯作者：
LEPPER, H
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N