Taams L S, van Eden W, Wauben M H
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
J Immunol. 1999 Feb 15;162(4):1974-81.
T cell anergy has been proposed as one of the mechanisms underlying peripheral T cell tolerance. In recent years, the functional relevance of T cell anergy has been studied extensively in vitro and in vivo, using different species, cell systems, and ways to induce anergy. Although these studies concurred about the induction of unresponsiveness, conflicting findings were obtained with respect to the function of anergic T cells and to the persistence of T cell anergy. In the present study, T cell anergy was induced through T-T presentation of the specific Ag by rat MHC class II+ T cells in the absence of professional APC. We show that, depending on the Ag dose with which T cells were incubated, distinct anergic phenotypes were induced. Incubation of T cell clones with a low (suboptimal) Ag dose induced hyporesponsiveness. Incubation with a higher (optimal) Ag dose induced an anergic state capable of exerting immunoregulatory effects. Incubation with a high (supraoptimal) Ag dose led to an anergic suppressive phenotype that was persistent and was not reversed by APC, Ag, and rIL-2. These findings demonstrate that T cell anergy is not confined to a single state of functional inactivation. Instead, multiple levels of T cell anergy exist. Thus, anergic T cells can contribute to the regulation of the immune response either in a persistent and active manner or in a passive manner, depending on their level of T cell anergy.
T细胞失能已被认为是外周T细胞耐受的潜在机制之一。近年来，T细胞失能的功能相关性已在体外和体内进行了广泛研究，采用了不同的物种、细胞系统以及诱导失能的方法。尽管这些研究在诱导无反应性方面达成了共识，但在失能T细胞的功能以及T细胞失能的持续性方面却得到了相互矛盾的结果。在本研究中，在没有专职抗原呈递细胞（APC）的情况下，通过大鼠MHC II类+ T细胞的T-T特异性抗原呈递来诱导T细胞失能。我们发现，根据与T细胞孵育的抗原剂量不同，会诱导出不同的失能表型。用低（次优）抗原剂量孵育T细胞克隆会诱导低反应性。用较高（最佳）抗原剂量孵育会诱导出一种能够发挥免疫调节作用的失能状态。用高（超最佳）抗原剂量孵育会导致一种持续存在且不会被APC、抗原和重组白细胞介素-2逆转的失能抑制表型。这些发现表明，T细胞失能并不局限于单一的功能失活状态。相反，存在多个层次的T细胞失能。因此，失能T细胞可以以持续且活跃的方式或被动方式，根据其失能水平对免疫反应的调节做出贡献。
