In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation

In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation
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DOI:
10.1182/blood.v90.11.4297.4297_4297_4306
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发表时间:
1997-12-01
期刊:
影响因子:
20.3
通讯作者:
Nadler, LM
Nadler, LM
中科院分区:
医学1区
文献类型:
--
作者:
Dorfman, DM;Schultze, JL;Nadler, LM

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B7家族共刺激分子在B细胞上的表达决定了其作为抗原呈递细胞(APC)的功能,不表达B7共刺激分子的B细胞诱导T细胞耐受,因此,B7共刺激分子在恶性肿瘤B细胞上的表达可能是其被抗肿瘤特异性T细胞识别的关键。在这里,我们发现,几乎所有的生发中心(GC)来源的B细胞淋巴瘤,包括滤泡性淋巴瘤(FL)和弥漫性大细胞淋巴瘤,但不是套细胞淋巴瘤或小淋巴细胞淋巴瘤(SLL/CLL),表达B7-1(CD 80)和B7-2(CD 86)在其细胞表面原位,虽然在极低的水平,尽管他们表达低水平的B7-1和B7-2,FL细胞不能诱导明显的同种异体T细胞增殖,但是FL上的B7共刺激分子似乎是功能性的,因为它们能够在二次同种异体混合淋巴细胞反应中增加预活化的T细胞的T细胞增殖。此外,低B7表达足以防止在体外诱导同种异体抗原特异性无能。因此,我们推测,虽然B7的低水平表达不足以启动生产性抗淋巴瘤T细胞反应,但可能足以防止体内T细胞耐受。(C)1997年,美国血液学会。
Expression of B7 family costimulatory molecules on B cells defines their capacity to function as antigen presenting cells (APCs), B cells that do not express B7 costimulatory molecules induce T-cell tolerance, Therefore, the expression of B7 costimulatory molecules on malignant B cells might be critical for their recognition by anti-tumor-specific T cells. Here we show that virtually all germinal center (GC)-derived B-cell lymphomas including follicular lymphoma (FL) and diffuse large cell lymphoma, but not mantle cell lymphoma or small lymphocytic lymphomas (SLL/CLL), express B7-1 (CD80) and B7-2 (CD86) on their cell surface in situ, although at extremely low levels, Despite their expression of low levels of B7-1 and B7-2, FL cells could not induce significant allogeneic T-cell proliferation, However, B7 costimulatory molecules on FL appeared to be functional because they were capable of increasing T-cell proliferation of preactivated T cells in a secondary allogeneic mixed lymphocyte response. Moreover, low B7 expression was sufficient to prevent the induction of alloantigen-specific anergy in vitro. Therefore, we postulate that whereas low-level expression of B7 is not sufficient to initiate a productive antilymphoma T-cell response, it might be sufficient to prevent T-cell tolerance in vivo. (C) 1997 by The American Society of Hematology.