Riedel S, Kraft M, Kucharzik T, Pauels H G, Tiemann M, Steinbüchel A, Domschke W, Lügering N
Dept. of Medicine B, Institute for Immunology and Institute for Microbiology, University of Münster, Germany.
Scand J Gastroenterol. 2001 Nov;36(11):1198-203. doi: 10.1080/00365520152584842.
Little is known about the function of T cells in the inflammatory infiltrate in Helicobacter pylori-associated gastritis and B-cell lymphoma of mucosa-associated lymphoid tissue (MALT type). Previous studies have proposed a dominant Th1-type response in low-grade MALT lymphoma consistent with the Th1 response observed in H. pylori-associated gastritis.
We performed a novel flow cytometric approach in which CD3 panning for enrichment and activation of small numbers of T cells and intracellular cytokine analysis were combined to selectively characterize the cytokine profile of T cells (IFN-gamma for Th1) derived from the gastric mucosa of 23 patients with low-grade MALT lymphoma stage IEI1 (lymphoma infiltration of mucosa/submucosa sparing the muscularis). Endosonography was performed in each case to control the depth of lymphoma infiltration. For comparison, 19 patients with H. pylori-positive gastritis were also analysed.
There was a CD4/CD8 ratio of 4 in patients with MALT lymphoma and of 2 in chronic gastritis. The proportion of IFN-gamma producing cells within the CD4-positive T-cell population in MALT lymphoma was 22%; in chronic gastritis it was 13% while no such difference could be encountered in CD8-positive T cells.
The data point towards a dominant intratumoral IFN-gamma dominated T-cell response associated with early low-grade MALT lymphoma. A polarized IFN-gamma dominated Th1-type response may either contribute to the inability of the immune system to eradicate H. pylori infection, thereby promoting the activation status of the lymphocytic infiltrate in low-grade MALT lymphoma, or may mirror a concomitant tumor-specific T-cell response accompanying early stages of tumor progression.
关于T细胞在幽门螺杆菌相关性胃炎及黏膜相关淋巴组织(MALT型)B细胞淋巴瘤炎症浸润中的作用,目前所知甚少。既往研究提出,低度MALT淋巴瘤中存在占主导地位的Th1型反应,这与幽门螺杆菌相关性胃炎中观察到的Th1反应一致。
我们采用了一种新型流式细胞术方法,将用于富集和激活少量T细胞的CD3淘选法与细胞内细胞因子分析相结合,以选择性地表征23例IEI1期低度MALT淋巴瘤患者(淋巴瘤浸润局限于黏膜/黏膜下层,未累及肌层)胃黏膜来源的T细胞(Th1型的干扰素-γ)的细胞因子谱。对每例患者进行内镜超声检查以控制淋巴瘤浸润深度。作为对照,还分析了19例幽门螺杆菌阳性胃炎患者。
MALT淋巴瘤患者的CD4/CD8比值为4,慢性胃炎患者为2。MALT淋巴瘤患者CD4阳性T细胞群体中产生干扰素-γ的细胞比例为22%;慢性胃炎患者为13%,而CD8阳性T细胞中未发现此类差异。
数据表明,早期低度MALT淋巴瘤存在以肿瘤内干扰素-γ为主导的T细胞反应。极化的以干扰素-γ为主导的Th1型反应可能要么导致免疫系统无法根除幽门螺杆菌感染,从而促进低度MALT淋巴瘤中淋巴细胞浸润的激活状态,要么反映肿瘤进展早期伴随的肿瘤特异性T细胞反应。