Riou Catherine, Dumont Alain R, Yassine-Diab Bader, Haddad Elias K, Sekaly Rafick-Pierre
Laboratoire d'Immunologie, Centre de recherche du CHUM, Pavillon Edouard-Asselin, Hôpital Saint-Luc, 264 René-Lévesque Boulevard E, Montréal, Québec H2X 1P1, Canada.
Int Immunol. 2006 Jun;18(6):827-35. doi: 10.1093/intimm/dxl019. Epub 2006 Apr 12.
It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation.
现已充分证实，细胞因子环境在对抗原的初次应答过程中会影响T淋巴细胞的激活、分化、增殖和死亡。我们利用体外模型，研究了在TCR刺激开始时添加的IL-4对初始CD8+ T细胞激活的表型和功能标志物的影响，这些标志物包括激活标志物的上调、增殖以及对激活诱导的细胞死亡（AICD）的易感性。我们报告称，与在初始CD8+ T细胞重复TCR刺激开始时添加的IL-2不同，IL-4可预防AICD，部分原因是其能够维持生存相关蛋白Bcl-2的水平。此外，在IL-4存在的情况下，TCR触发的初始CD8+ T细胞激活会导致一个CD8+ T细胞亚群的发育，该亚群能够正常增殖，但无法表现出诸如CD25和颗粒酶B上调等特征性激活参数。综上所述，这些结果表明，在初次激活过程中暴露于IL-4会通过诱导产生一群抗AICD、具有增殖能力但不表现出某些CD8+ T细胞激活典型特征的细胞来影响CD8+ T细胞的分化。
