Umetsu D T, Esserman L, Donlon T A, DeKruyff R H, Levy R
Department of Medicine, Stanford University School of Medicine, CA 94305.
J Immunol. 1990 Apr 1;144(7):2550-7.
We examined stimuli which are required for the induction of in vitro proliferation of follicular lymphoma cells, a low grade non-Hodgkin's B cell lymphoma characterized by a specific chromosomal translocation, t(14;18)(q32;q21), and by in vivo growth of the lymphoma cells in germinal center-like follicles infiltrated with CD4+ T cells. The purified follicular lymphoma cells, which are morphologically uniform, small, and dense, did not respond to stimulation with soluble lymphokines in the absence of T cells. Vigorous in vitro proliferation of follicular lymphoma cells was induced, however, when the follicular lymphoma cells were cultured with a CD4+ T cell clone which recognized alloantigens expressed by the lymphoma cells. This response required B-T cell contact, and was inhibited by anti-class II but not by anti-class I MHC mAb, indicating that these neoplastic B cells behaved as normal B cells and responded to normal activation and differentiation signals from T cells. After the cognate B lymphoma-T cell interaction occurred in culture, addition of IL-2 or IL-4 enhanced the proliferation of the tumor cells. These results, with a monoclonal and homogeneous population of B cells, affirm the idea that cognate interaction between B cells and Th cells is required for the effective activation of resting B cells. Moreover, these results suggest that a critical host-tumor interaction occurs in vivo, and that the polyclonal CD4+ T cells that infiltrate follicular lymphomas play a role in sustaining rather than inhibiting tumor growth in vivo. If so, therapies directed not only against the neoplastic cell but also against specific T cells and their cognate interactions with tumor cells may have a rationale.
我们研究了诱导滤泡性淋巴瘤细胞体外增殖所需的刺激因素。滤泡性淋巴瘤是一种低度恶性非霍奇金B细胞淋巴瘤，其特征为特定的染色体易位t(14;18)(q32;q21)，以及淋巴瘤细胞在充满CD4+T细胞的生发中心样滤泡中的体内生长。纯化后的滤泡性淋巴瘤细胞形态均一、体积小且致密，在没有T细胞的情况下，对可溶性淋巴因子的刺激无反应。然而，当滤泡性淋巴瘤细胞与识别淋巴瘤细胞表达的同种抗原的CD4+T细胞克隆共同培养时，可诱导其在体外剧烈增殖。这种反应需要B细胞与T细胞接触，且可被抗II类但不能被抗I类MHC单克隆抗体抑制，这表明这些肿瘤性B细胞表现得如同正常B细胞，并对来自T细胞的正常激活和分化信号产生反应。在培养物中发生同源性B淋巴瘤 - T细胞相互作用后，添加IL - 2或IL - 4可增强肿瘤细胞的增殖。这些结果，基于单克隆且均一的B细胞群体，证实了静止B细胞的有效激活需要B细胞与Th细胞之间同源性相互作用这一观点。此外，这些结果表明在体内发生了关键的宿主 - 肿瘤相互作用，并且浸润滤泡性淋巴瘤的多克隆CD4+T细胞在维持而非抑制体内肿瘤生长中发挥作用。如果是这样，不仅针对肿瘤细胞，而且针对特定T细胞及其与肿瘤细胞的同源性相互作用的治疗方法可能具有合理性。
