Taams L S, van Rensen A J, Poelen M C, van Els C A, Besseling A C, Wagenaar J P, van Eden W, Wauben M H
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Eur J Immunol. 1998 Sep;28(9):2902-12. doi: 10.1002/(SICI)1521-4141(199809)28:09<2902::AID-IMMU2902>3.0.CO;2-B.
We here show that anergic T cells are active mediators of T cell suppression. In co-culture experiments, we found that anergic T cells, derived from established rat T cell clones and rendered anergic via T cell presentation of the specific antigen (Ag), were active inhibitors of T cell responses. Anergic T cells inhibited not only the responses of T cells with the same Ag specificity as the anergic T cells, but were also capable of efficiently inhibiting polyclonal T cell responses directed to other epitopes. This suppression required close cell-cell contact between antigen-presenting cells (APC), anergic T cells and responder T cells, and only occurred when the epitope recognized by the anergic T cell was present. The suppression was not caused by passive competition for ligands on the APC surface, IL-2 consumption, or cytolysis, and was not mediated by soluble factors derived from anergic T cells that were stimulated with their specific Ag. When responder T cells were added 24 h after co-culturing anergic cells in the presence of Ag and APC, T cell responses were still suppressed, indicating that the suppressive effect was persistently present. However, anergic T cells were not able to suppress responder T cells that had already received a full activation signal. We propose that suppression by anergic T cells is mediated via the APC, either through modulation of the T cell-activating capacity of the APC (APC/T cell interaction), or by inhibition of T cells recognizing their ligand in close proximity on the same APC (T/T cell interaction).
我们在此表明，无反应性T细胞是T细胞抑制的活性介质。在共培养实验中，我们发现，源自已建立的大鼠T细胞克隆并通过特异性抗原（Ag）的T细胞呈递而变得无反应性的无反应性T细胞，是T细胞反应的活性抑制剂。无反应性T细胞不仅抑制与无反应性T细胞具有相同Ag特异性的T细胞的反应，而且还能够有效抑制针对其他表位的多克隆T细胞反应。这种抑制需要抗原呈递细胞（APC）、无反应性T细胞和反应性T细胞之间紧密的细胞-细胞接触，并且仅在无反应性T细胞识别的表位存在时才会发生。这种抑制不是由对APC表面配体的被动竞争、IL-2消耗或细胞溶解引起的，也不是由用其特异性Ag刺激的无反应性T细胞衍生的可溶性因子介导的。当在Ag和APC存在下将反应性T细胞在共培养无反应性细胞24小时后加入时，T细胞反应仍然受到抑制，表明抑制作用持续存在。然而，无反应性T细胞无法抑制已经接收到完全激活信号的反应性T细胞。我们提出，无反应性T细胞的抑制是通过APC介导的，要么通过调节APC的T细胞激活能力（APC/T细胞相互作用），要么通过抑制在同一APC上紧密接近识别其配体的T细胞（T/T细胞相互作用）。
