Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.

Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.
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主动抑制怀孕小鼠的宿主抗移植物反应。

DOI:
10.4049/jimmunol.134.3.1659
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发表时间:
1985
影响因子:
4.4
通讯作者:
K. Rosenthal
K. Rosenthal
中科院分区:
医学2区
文献类型:
--
作者:
D. Clark;A. Chaput;C. Walker;K. Rosenthal

文献摘要

被引文献

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哺乳动物胎儿表达多种抗原,母体免疫系统可以针对这些抗原反应,并且在同种异体交配中携带父本移植抗原。虽然这些抗原可以表达在与母体子宫蜕膜接触的胎儿滋养层细胞上,但“胎儿同种异体移植物”通常不会被排斥。先前的研究已经证明了非特异性非胸腺衍生的抑制细胞的存在下,在淋巴结引流子宫和蜕膜的实验室小鼠进行第一次异基因妊娠。这些抑制细胞似乎是小淋巴细胞,其在体外和体内抑制细胞毒性T淋巴细胞(CTL)的产生,并且当在体外37 ℃培养48小时时阐述非特异性非MHC限制性可溶性抑制活性。我们现在报告说,可溶性抑制活性从蜕膜(DS)的同种异体妊娠C3 H/HeJ小鼠抑制初级和二级(记忆)CTL反应在体外,但不抑制裂解的靶细胞由预先形成的CTL。DS不抑制YAC淋巴瘤细胞、P-815细胞或C3 H胎盘滋养母细胞瘤细胞系的增殖。抑制活性从蜕膜中的抗thy-1.2 +补体抗性细胞获得,也可以从同种异体妊娠的CD 1 nu/nu小鼠的蜕膜获得,并且与Sephacryl 200色谱上约100,000道尔顿的单峰活性相关。在体外混合淋巴细胞培养中加入IL 2粗品或HPLC纯化的抑制因子均不能克服IL 2的抑制作用,而抑制因子粗品和柱纯化的抑制因子均能抑制IL 2依赖的NK细胞系H Y细胞的增殖。此外,DS抑制IL 2依赖的细胞毒性效应细胞在体外产生的异基因刺激细胞的情况下。因此,从成功同种异体妊娠小鼠蜕膜中存在的非T细胞中获得的可溶性抑制因子可以阻断对IL 2的反应,并抑制特异性和非特异性细胞毒性效应细胞的产生。讨论了这种抑制对“胎儿同种异体移植物”存活的意义。
The mammalian fetus expresses a variety of antigens against which the maternal immune system can react and which in an allogeneic mating bears paternal transplantation antigens. Although these antigens may be expressed on the fetal trophoblast cells that contact maternal uterine decidua, the "fetal allograft" is not usually rejected. Previous studies have demonstrated the presence of nonspecific non-thymus-derived suppressor cells in the lymph nodes draining the uterus and in decidua of laboratory mice undergoing first allogeneic pregnancy. These suppressor cells appeared to be small lymphocyte cells that inhibit the generation of cytotoxic T lymphocytes (CTL) in vitro and in vivo and elaborate a nonspecific non-MHC-restricted soluble suppressor activity when cultured for 48 hours at 37 degrees C in vitro. We now report that soluble suppressor activity obtained from the decidua (DS) of allopregnant C3H/HeJ mice inhibits both the primary and secondary (memory) CTL response in vitro but does not inhibit lysis of target cells by preformed CTL. DS did not suppress the proliferation of YAC lymphoma cells, P-815 cells, or a C3H placental trophoblastoma line. Suppressor activity was obtained from anti-thy-1.2 + complement-resistant cells in the decidua, could also be obtained from the decidua of allopregnant CD1 nu/nu mice, and was associated with a single peak of activity of approximately 100,000 daltons on Sephacryl 200 chromatography. Suppression could not be overcome by adding either crude or HPLC-purified IL 2 to the mixed lymphocyte cultures in vitro, and both crude and column-purified suppressor factor inhibited the IL 2-dependent proliferation of H-Y cells (a cloned T cell line with NK activity). Furthermore, DS inhibited the IL 2-dependent generation of cytotoxic effector cells in vitro in the absence of allogeneic stimulator cells. Thus, a soluble suppressor factor obtained from non-T cells present in the decidua of successfully allopregnant mice could block the response to IL 2 and inhibit the generation of both specific and nonspecific cytotoxic effector cells. The significance of this inhibition with respect to survival of the "fetal allograft" is discussed.