DISSECTION OF SUPPRESSOR-CELL GENERATION INVITRO

DISSECTION OF SUPPRESSOR-CELL GENERATION INVITRO
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DOI:
10.1016/0198-8859(86)90285-5
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发表时间:
1986-11-01
期刊:
影响因子:
2.7
通讯作者:
WERNET, P
WERNET, P
中科院分区:
医学4区
文献类型:
--
作者:
PAWELEC, G;SCHNEIDER, EM;WERNET, P

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外周血单核细胞培养后,发现非特异性抑制淋巴增殖反应的细胞(SC):(1)抑制T细胞克隆,(2)混合淋巴细胞培养(MLC),(3)重组白介素2(IL-2),但单独培养后未发现。抗IL-2受体(R)的单抗TU69可阻断依赖IL-2的T细胞株的LP反应,也可阻断T细胞克隆对SC的诱导,但完全不能抑制MLC或IL-2诱导的SC生成。提示TU69定义的IL-2R表位不参与后一系统中SC的诱导。抗HLA-DQ Tu22-DR(TU34,SG157)、-DP(B7/21)或DR和DP TU43,58的单抗均能阻断适当特定克隆的刺激,但不能阻断所研究的三种系统中的任何一种SC的诱导。相比之下,广泛反应的Moab TU39至少与DR和DP结合,但也对暂定为“DY”的决定簇具有额外的反应性,阻止了T细胞克隆和MLC对SC的诱导。最后,抗人类白细胞抗原I类摩押,W6/32。HL可显著减少MLC的SC生成,但对rIL-2或T细胞克隆无明显影响。因此,非特异性SC的诱导被分成三条途径:(1)I类和TU39类决定簇,而不是DR、DQ或DP决定簇(在MLC中),它独立于TU69结合的IL-2R表位;(2)只有TU39定义的决定簇(带有T细胞克隆),它们依赖于IL 2R;(3)既不是I类、II类也不是TU39定义的决定簇(由rIL-2诱导),它也不是TU69+IL-2R独立的。
Suppressor cells (SC) that nonspecifically inhibited lymphoproliferative (LP) responses were found after culturing peripheral blood mononuclear cells: (1) with suppressor T-cell clones, (2) in mixed lymphocyte cultures (MLC), and (3) with recombinant interleukin 2 (IL-2), but were not found after culture in medium alone. A monoclonal anti-IL-2 receptor (R) antibody (MoAb), TU69 which blocked LP responses of IL 2-dependent T-cell lines, also blocked SC induction by T-cell clones, but completely failed to inhibit SC generation in MLC or with IL-2. This suggests that the IL-2R epitope defined by TU69 was not involved in SC indution in the latter systems. MoAb against HLA-DQ TU22 -DR (TU34, SG157), -DP (B7/21), or DR and DP TU43, 58), all of which were able to block stimulation of appropriately specific clones, did not block SC induction in any of the three systems studied. In contrast, the broadly reactive moAB TU39, which binds at least DR and DP but also has additional reactivity for determinants tentatively designated "DY," blocked SC induction by T-cell clones and in MLC. Finally, an anti-HLA class I MoAb, W6/32. HL, greatly decreased SC generation in MLC, but not with rIL-2 or T-cell clones. Thus, the induction of nonspecific SC was dissected into three pathway involving: (1) class I and TU39-defined but not DR, DQ, or DP determinants (in MLC) which was independent of the IL-2R epitope bound by TU69; (2) only TU39-defined determinants (with T-cell clones), which were IL 2R dependent; and (3) neither class I, class II nor TU39-defined determiants (induction by rIL-2), which was also TU69 + IL-2R independent.