Wan Ni, Dai Hehua, Wang Tao, Moore Yolonda, Zheng Xin Xiao, Dai Zhenhua
Center for Biomedical Research, University of Texas Health Center, Tyler, TX 75708, USA.
J Immunol. 2008 Jan 1;180(1):113-21. doi: 10.4049/jimmunol.180.1.113.
Memory T cells respond faster and more vigorously than their naive counterparts and are critical for adaptive immunity. However, it is unknown whether and how memory T cells react in the face of irrelevant Ags. It is generally accepted that bystander memory T cells are neutral in immune responsiveness. In this study, we present the first evidence that bystander central memory (TCM), but not effector memory (TEM), CD8+ T cells suppress allograft rejection as well as T cell proliferation in the draining lymph nodes (DLN) of recipient mice. Both bystander TCM and naive T cells, but fewer TEM cells, migrated to DLN, whereas TCM cells exhibited faster turnover than their naive counterparts, suggesting that bystander TCM cells have an advantage over their naive counterparts in suppression. However, bystander TEM cells migrated to inflammatory graft sites, but not DLN, and yet failed to exert their suppression. These findings indicate that bystander memory T cells need to migrate to lymph nodes to exert their suppression by inhibiting responder T cell activation or homeostatic proliferation. Moreover, the suppression mediated by bystander TCM cells was largely dependent on IL-15, as IL-15 was required for their homeostatic proliferation and TCM-mediated suppression of allograft rejection. This suppression also required the presence of TGFbeta1, as TCM cells expressed TGFbeta1 while neutralizing TGFbeta1 abolished their suppression. Thus, bystander TCM, but not TEM, CD8+ T cells are potent suppressors rather than bystanders. This new finding will have an impact on cellular immunology and may have clinic implications for tolerance induction.
记忆性T细胞比其初始对应细胞反应更快、更强烈，对适应性免疫至关重要。然而，尚不清楚记忆性T细胞面对无关抗原时是否以及如何做出反应。人们普遍认为旁观者记忆性T细胞在免疫反应性方面是中性的。在本研究中，我们首次提供证据表明，旁观者中枢记忆性（TCM）而非效应记忆性（TEM）CD8⁺T细胞可抑制受体小鼠引流淋巴结（DLN）中的同种异体移植排斥反应以及T细胞增殖。旁观者TCM细胞和初始T细胞均迁移至DLN，但迁移至DLN的TEM细胞较少，而TCM细胞的更新速度比其初始对应细胞更快，这表明旁观者TCM细胞在抑制作用方面比其初始对应细胞具有优势。然而，旁观者TEM细胞迁移至炎症性移植部位而非DLN，但未能发挥其抑制作用。这些发现表明，旁观者记忆性T细胞需要迁移至淋巴结，通过抑制反应性T细胞活化或稳态增殖来发挥其抑制作用。此外，旁观者TCM细胞介导的抑制作用在很大程度上依赖于IL-15，因为IL-15是其稳态增殖和TCM介导的同种异体移植排斥反应抑制所必需的。这种抑制作用还需要TGFβ1的存在，因为TCM细胞表达TGFβ1，而中和TGFβ1会消除其抑制作用。因此，旁观者TCM而非TEM CD8⁺T细胞是有效的抑制细胞而非旁观者。这一新发现将对细胞免疫学产生影响，可能对诱导耐受性具有临床意义。
