INSERM, France.
J Immunol. 2010 Jan 1;184(1):134-40. doi: 10.4049/jimmunol.0901980. Epub 2009 Nov 30.
gammadelta T lymphocytes are attractive effector cells for immunotherapy. In vitro, they can be expanded and kill efficiently a variety of tumor cells. The frequency and distribution of gammadelta T lymphocytes were compared in tumor lymph nodes of 51 patients with follicular lymphoma lymph nodes (FL-LNs) and 28 patients with inflammatory lymph nodes (I-LNs). gammadelta and CD8 T lymphocytes were less abundant in FL-LNs than in I-LNs (p <or= 10(-7)). These lymphocytes were localized in the perifollicular zone outside of the tumor follicles. Perifollicular gammadelta T lymphocytes expressed CCR7, in contrast to peripheral blood gammadelta T lymphocytes and both perifollicular and peripheral blood gammadelta T lymphocytes expressed CXCR4. The very low number of perifollicular gammadelta T lymphocytes in FL-LNs could be explained in part by migratory problems because of absence of CCL19 expression in FL-LNs compared with I-LNs. Conversely, CCL21 and CXCL12 were similarly expressed in both FL-LNs and I-LNs. CCL19 and CCL21 were expressed in high endothelial venules and lymphatic vessels, whereas CXCL12 was expressed by stromal cells surrounding high endothelial venules and lymphatic vessels. Peripheral gammadelta T lymphocytes from 34 patients with FL, expanded with Phosphostim and IL-2 in vitro, had the same expansion capacity as those from healthy individuals. Thus, gammadelta T lymphocytes can be an attractive source for adoptive immunotherapy in patients with FL, providing they may home in tumor LNs.
γδ T 淋巴细胞是免疫治疗的有吸引力的效应细胞。在体外,它们可以被扩增并有效地杀死各种肿瘤细胞。比较了 51 例滤泡性淋巴瘤淋巴结(FL-LN)和 28 例炎症性淋巴结(I-LN)患者的肿瘤淋巴结中γδ T 淋巴细胞和 CD8 T 淋巴细胞的频率和分布。FL-LN 中的γδ和 CD8 T 淋巴细胞比 I-LN 中的少(p<10(-7))。这些淋巴细胞定位于肿瘤滤泡外的滤泡周围区。与外周血 γδ T 淋巴细胞相比,滤泡周围 γδ T 淋巴细胞表达 CCR7,而外周血 γδ T 淋巴细胞和滤泡周围及外周血 γδ T 淋巴细胞均表达 CXCR4。FL-LN 中滤泡周围 γδ T 淋巴细胞数量非常少,部分原因可能是由于 FL-LN 中 CCL19 的表达缺失,导致迁移问题。相反,CCL21 和 CXCL12 在 FL-LN 和 I-LN 中均有相似的表达。CCL19 和 CCL21 在高内皮静脉和淋巴管中表达,而 CXCL12 则由围绕高内皮静脉和淋巴管的基质细胞表达。来自 34 例 FL 患者的外周 γδ T 淋巴细胞,用 Phosphostim 和 IL-2 体外扩增,其扩增能力与健康个体相同。因此,γδ T 淋巴细胞可以成为 FL 患者过继免疫治疗的有吸引力的来源,前提是它们可能归巢到肿瘤 LN 中。