Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells.

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells.
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人类的免疫调节 T 细胞。

DOI:
10.1172/jci111743
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发表时间:
1985
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Engleman,EG
Engleman,EG
中科院分区:
--
文献类型:
--
作者:
Sansoni,P;Silverman,ED;Khan,MM;Melmon,KL;Engleman,EG

文献摘要

被引文献

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组胺介导的人体免疫应答抑制的一种机制是激活携带Leu 2(OKT 8)标记的T抑制细胞。目前的研究是利用单克隆抗体(9.3)来表征组胺诱导的抑制细胞,该单克隆抗体先前显示可以区分细胞毒性T细胞和抗原特异性抑制性T细胞。从外周血中分离的Leu 2+细胞进一步用抗体9.3分离为Leu 2+,9.3+和Leu 2+,9.3-亚群,每个亚群与不同浓度的组胺孵育,然后测定它们在体外抑制免疫应答的能力。结果表明,Leu 2+,9.3-亚群包括所有组胺诱导的抑制细胞,10(-4)M组胺是抑制细胞诱导的最佳浓度,Leu 2+,9.3-细胞暴露于组胺30 s足以启动诱导过程。用组胺处理后,这些细胞抑制植物血凝素诱导的T细胞增殖和美洲商陆有丝分裂原诱导的B细胞分化。抑制植物血凝素诱导的增殖是抵抗X射线照射与1,200拉德,无论是在组胺暴露之前或之后,表明Leu 2+,9.3-细胞不需要增殖成为抑制细胞或施加抑制。此外,这些细胞的抑制不是由于反应动力学的改变。最后,组胺2型受体拮抗剂(西咪替丁),但不是1型受体拮抗剂(美托咪定)阻断抑制细胞的诱导。根据这些结果和我们以前的抗原特异性抑制细胞的研究,我们得出结论,Leu 2+抑制细胞在人是从一个前体池,是从细胞分化成细胞毒性T细胞的细胞表型不同。
One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells.