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Proliferation of human lymphoid malignancy by the Interaction of follicular dendritic cells

滤泡树突状细胞相互作用导致人类淋巴恶性肿瘤的增殖

基本信息

批准号：
15591038
负责人：
KAGAMI Yoshitoyo
金额：
$ 2.18万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Germinal center B cells are differentiated with the help of follicular dendritic cells(FDC), and follicular lymphoma(FL) also contain substantial FDC. To clarify the interaction between FL and FDC, FDC like cell line HK was co-cultured with FL. HK did not support the growth of FL cells sufficiently, however, in the presence of the mixture of IL-2, IL-4, IL-7, and IL-15,HK supported exclusively the growth of CD4(+) T cells which existed in FL. After a month, cell number highly increased more than 1000 folds. These data indicated that HK cells supported the growth of CD4(+) T cells in the presence of IL-2, IL-4, IL-7 and IL-15. Then, to confirm whether HK cells stimulate the growth of CD4(+) T-lymphoma or not, lymph node of three Adult T-cell leukemia/lymphoma(ATLL) were co-cultured with HK and IL-2,4,7,15. In all three cases, CD4(+) T-cells proliferate vigorously more than 3 months. One of three cells was derived from original lymphoma cells by using T-cell receptor gamma chain rearrangement pattern. This ATLL derived cell line is dependent on HK, because without HK, it stopped to proliferate a few weeks later and finally died. These data suggested that some of Adult T-cell leukemia/lymphoma, FDC provide the favorable environment for its growth in the course of the interaction of FDC and T-cells. In order to confirm whether other T-cell lymphomas are stimulated by HK or not, some T-cell lymphoma cells were co-cultured with HK cells. Among them, two of three angioimmunoblastic T-cell lymphoma also proliferated on the HK cells in the presence of IL-2, IL-4, IL-7 and IL-15. The clonal band of the original lymphoma cells was conserved in the growing cells. These data indicated in the lymph node, FDCs afford favorable environment to proliferate several types of malignant lymphoma.

在滤泡树突状细胞（FDC）的帮助下，生殖中心B细胞分化，并且滤泡性淋巴瘤（FL）也含有大量FDC。为了阐明FL和FDC之间的相互作用，将FDC样细胞系HK与FL共培养，HK不能充分支持FL细胞的生长，但在IL-2、IL-4、IL-7和IL-15的混合物存在下，HK只支持FL中存在的CD 4（+）T细胞的生长，一个月后细胞数增加了1000倍以上。这些数据表明HK细胞在IL-2、IL-4、IL-7和IL-15存在下支持CD 4（+）T细胞的生长。然后，为了证实HK细胞是否刺激CD 4（+）T淋巴瘤的生长，将三个成人T细胞白血病/淋巴瘤（ATLL）的淋巴结与HK和IL-2，4，7，15共培养。在所有三种情况下，CD 4（+）T细胞增殖活跃超过3个月。其中一个细胞来源于原始淋巴瘤细胞，采用T细胞受体γ链重排模式。这种ATLL衍生的细胞系依赖于HK，因为没有HK，它在几周后停止增殖并最终死亡。提示某些成人T细胞白血病/淋巴瘤，FDC在与T细胞相互作用的过程中为其生长提供了有利的环境。为了证实其他T细胞淋巴瘤是否受HK刺激，将一些T细胞淋巴瘤细胞与HK细胞共培养。其中，在IL-2、IL-4、IL-7和IL-15的存在下，三种血管免疫母细胞性T细胞淋巴瘤中的两种也在HK细胞上增殖。原始淋巴瘤细胞的克隆带在生长细胞中是保守的。这些数据表明，在淋巴结，FDCs提供了良好的环境，增殖的几种类型的恶性淋巴瘤。