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体内抗半抗原抗体反应的调节:记忆性、载体特异性Lyt-2⁺ T细胞可终止抗体产生而不改变反应峰值。

Regulation of anti-hapten antibody responses in vivo: memory, carrier-specific Lyt-2+ T cells can terminate antibody production without altering the peak of response.

作者信息

Kanellopoulos-Langevin C, Mathieson B J, Perkins A, Maynard A, Asofsky R

出版信息

J Immunol. 1984 Apr;132(4):1639-46.

PMID:6199405
Abstract

By using the classical hapten-carrier antigenic system (dinitrophenyl-keyhole limpet hemocyanin) (DNP-KLH), and positive immunoselective techniques for purification of lymphocyte subsets, we studied the kinetics and role of KLH-primed T cells in the termination of a secondary in vivo plaque-forming cell (PFC) response against DNP in the mouse. Separation of T cells by Lyt-2 phenotype and recombination of T cell subsets demonstrated that a single injection of KLH in complete Freund's adjuvant (CFA) concomitantly generated both helper and suppressor T cells in the spleens of primed mice. When these KLH-primed, purified T cells were transferred into irradiated recipients along with DNP-primed, purified B cells and DNP-KLH, helper activity was demonstrable first, with the early production of a high anti-DNP PFC response. Suppression of the PFC response was observed only after the response had fully developed; the PFC response was then "terminated" within a few days. Helper activity was obtained with the carrier-primed Lyt-2- T cell population, whereas suppression required the addition of Lyt-2+ T cells. Both activities were generated over a wide dose range, were specific for the priming antigen KLH, and could be detected as early as 8 days or as late as 9 mo after a single priming injection of KLH. Lyt-2+ T cells from unprimed donors or from animals primed with a different carrier did not have the capacity to terminate the response when added with the primed Lyt-2- helper T cells. Thus, we have now demonstrated the existence of carrier-specific, long-lived, "memory" suppressor T cells, which are initially generated in parallel with specific helper T cells. Whereas these memory suppressor T cells do not inhibit the induction of a secondary antibody response, they can effectively terminate it once it has developed, and may therefore account for the normal termination of antibody responses.

摘要

通过使用经典的半抗原-载体抗原系统(二硝基苯基-钥孔戚血蓝蛋白)(DNP-KLH),以及用于纯化淋巴细胞亚群的阳性免疫选择技术,我们研究了经KLH预致敏的T细胞在终止小鼠体内针对DNP的二次空斑形成细胞(PFC)反应中的动力学及作用。通过Lyt-2表型分离T细胞并重组T细胞亚群表明,在完全弗氏佐剂(CFA)中单次注射KLH可在预致敏小鼠的脾脏中同时产生辅助性T细胞和抑制性T细胞。当将这些经KLH预致敏、纯化的T细胞与经DNP预致敏、纯化的B细胞以及DNP-KLH一起转移至受辐照的受体中时,首先可证明有辅助活性,同时早期会产生高抗DNP PFC反应。仅在反应充分发展后才观察到PFC反应的抑制;然后PFC反应在几天内“终止”。经载体预致敏的Lyt-2-T细胞群体可获得辅助活性,而抑制则需要添加Lyt-2+T细胞。两种活性均在较宽的剂量范围内产生,对预致敏抗原KLH具有特异性,并且在单次预致敏注射KLH后最早8天或最晚9个月均可检测到。来自未预致敏供体或用不同载体预致敏动物的Lyt-2+T细胞在与预致敏的Lyt-2-辅助性T细胞一起添加时没有终止反应的能力。因此,我们现已证明存在载体特异性、长寿的“记忆”抑制性T细胞,它们最初与特异性辅助性T细胞并行产生。虽然这些记忆抑制性T细胞不抑制二次抗体反应的诱导,但它们一旦反应发展就可以有效地终止它,因此可能是抗体反应正常终止的原因。

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