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辅助性T细胞克隆产生一种抗原特异性分子(T-ABM),其在抑制诱导中起作用。

A helper T cell clone produces an antigen-specific molecule (T-ABM) which functions in the induction of suppression.

作者信息

Green D R, Chue B, Zheng H G, Ferguson T A, Beaman K D, Flood P M

机构信息

Department of Pathology, Yale University School of Medicine, New Haven, CT.

出版信息

J Mol Cell Immunol. 1987;3(2):95-108.

PMID:2978240
Abstract

Among Ly-1+,2-T cells there appears to be two independent modes of antigen recognition. Helper and cytotoxic Ly-1 T cells recognize antigen only in the context of I region products whereas regulatory T cells, such as T suppressor inducer cells, produce antigen-specific, antigen-binding molecules (T-ABM). These T-ABM often have been found to form a part of biologically active, antigen-specific regulatory factors. A number of environmental conditions effect whether a foreign antigen will produce a positive response leading to immunity or a negative one leading to tolerance. Many of the conditions which favor the induction of suppressor T cells simultaneously preclude the proper interaction of antigen presenting cells with helper T cells. This parallel led us to ask whether helper T cells perform at least two, apparently opposite functions: a) under conditions favoring immunity helper T cells produce lymphokines to activate immune effector cells, and b) under conditions favoring suppression they produce molecules which function in suppressor cell induction. Therefore, this question relates to the mechanisms by which an immune response is switched into either a positive (help) or negative (suppressive) track. In addition, it begins to address the relationship between the different modes of antigen recognition exhibited by helper T cells vs. T suppressor inducer cells (see above). To explore this problem we employed an antigen-specific, I-Ak restricted helper T cell clone as the purest available source of helper T cells. We presented antigen to the cloned T cells under conditions which favor suppression rather than help (for example, by ultraviolet irradiation of the antigen-presenting cells) and collected supernatants 48 hrs later. The supernatants were then examined for activity in a functional assay for antigen-specific suppressor factors. Our results indicate that under conditions favoring suppression, a T-ABM was produced which functioned in the antigen-specific induction of suppression in vitro. The T-ABM had the same antigen specificity as that exhibited by the helper T cell and was therefore probably derived from the clone. This observation introduces the possibility that the interaction between antigen-presenting cells and helper T cells is a crucial decision point in the immune response which can lead to either immunity or suppression. The latter would be achieved through the production, by helper T cells, of an antigen-specific component of T suppressor inducer factor (i.e., the T-ABM). The possible relationship between T-ABMs and the T cell receptor is discussed.

摘要

在Ly-1⁺、2⁻T细胞中,似乎存在两种独立的抗原识别模式。辅助性和细胞毒性Ly-1 T细胞仅在I区产物的背景下识别抗原,而调节性T细胞,如抑制性诱导细胞,会产生抗原特异性的抗原结合分子(T-ABM)。这些T-ABM常常被发现构成生物活性的、抗原特异性调节因子的一部分。许多环境条件会影响外来抗原是产生导致免疫的阳性反应还是导致耐受的阴性反应。许多有利于抑制性T细胞诱导的条件同时会排除抗原呈递细胞与辅助性T细胞的正常相互作用。这种平行关系促使我们思考辅助性T细胞是否至少执行两种明显相反的功能:a)在有利于免疫的条件下,辅助性T细胞产生淋巴因子以激活免疫效应细胞;b)在有利于抑制的条件下,它们产生在抑制性细胞诱导中起作用的分子。因此,这个问题涉及免疫反应转变为阳性(辅助)或阴性(抑制)途径的机制。此外,它开始探讨辅助性T细胞与抑制性诱导细胞所表现出的不同抗原识别模式之间的关系(见上文)。为了探究这个问题,我们使用了一个抗原特异性的、I-Ak限制的辅助性T细胞克隆,作为最纯净的辅助性T细胞来源。我们在有利于抑制而非辅助的条件下(例如,通过紫外线照射抗原呈递细胞)将抗原呈递给克隆的T细胞,并在48小时后收集上清液。然后在上清液中检测其在抗原特异性抑制因子功能测定中的活性。我们的结果表明,在有利于抑制的条件下,会产生一种T-ABM,它在体外抗原特异性抑制诱导中起作用。该T-ABM与辅助性T细胞表现出相同的抗原特异性,因此可能来源于该克隆。这一观察结果提出了一种可能性,即抗原呈递细胞与辅助性T细胞之间的相互作用是免疫反应中的一个关键决策点,它可以导致免疫或抑制。后者将通过辅助性T细胞产生抑制性诱导因子的抗原特异性成分(即T-ABM)来实现。文中还讨论了T-ABM与T细胞受体之间可能的关系。

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