Department of Medical Microbiology and Immunology, University of Toledo Medical College, Toledo, OH 43614, United States.
Immunol Lett. 2010 Feb 16;128(2):116-23. doi: 10.1016/j.imlet.2009.12.019. Epub 2010 Jan 11.
Multiple activation signals (including antigen, co-stimulation, and cytokines) during T-cell priming affect the subsequent generation of memory T cells, whose survival is maintained by IL-7 and IL-15. Since the IL-7 receptor is highly expressed not only on the surface of memory T cells but also on naïve T cells, we propose that early exposure to IL-7 during priming of naïve T cells may promote their survival, and thus enhances the generation of memory cells. To test this hypothesis, TCR transgenic OT-II CD4(+) T cells were stimulated in vitro with OVA(323-339) peptide presented by syngeneic antigen-presenting cells (APCs). IL-7 or an IL-7 like cytokine, thymic stromal lymphopoietin (TSLP), was added at the initial 2-day cultivation stage. We found that a short exposure to IL-7 or TSLP during priming did not affect activation, proliferation, and glucose uptake by CD4(+) T cells compared to controls when examined on culture day 6. However, the same 6-day cultures showed that IL-7 (but not TSLP) significantly decreased the frequency of apoptotic CD4(+) T cells compared to controls. More importantly, an adoptive transfer of the 6-day primed OT-II T cells into CD45.1(+) congenic mice demonstrated that IL-7 (but not TSLP) elevated by 3- and 4-fold the number of transferred CD4(+) T cells in spleen (p<0.05) and lymph nodes (p<0.05), respectively, compared to controls. Almost all transferred CD4(+) T populations displayed phenotypes of effector (CD44(+)CD62L(-)) or central (CD44(+)CD62L(+)) memory T cells. We thus conclude that exposure of CD4(+) T cells to IL-7 during priming results in an increased frequency of CD4(+) memory T cells.
多种激活信号（包括抗原、共刺激和细胞因子）在 T 细胞启动时会影响记忆 T 细胞的后续生成，而记忆 T 细胞的存活则由 IL-7 和 IL-15 维持。由于 IL-7 受体不仅在记忆 T 细胞表面高度表达，而且在初始 T 细胞表面也高度表达，我们提出在初始 T 细胞启动时早期暴露于 IL-7 可能促进其存活，从而增强记忆细胞的生成。为了验证这一假说，我们用 OVA(323-339)肽体外刺激 TCR 转基因 OT-II CD4(+)T 细胞，并用同种抗原呈递细胞 (APC) 呈递。在最初的 2 天培养阶段添加 IL-7 或类似 IL-7 的细胞因子胸腺基质淋巴细胞生成素 (TSLP)。我们发现，与对照组相比，在启动阶段短暂暴露于 IL-7 或 TSLP 对 CD4(+)T 细胞的激活、增殖和葡萄糖摄取没有影响，直到第 6 天的培养。然而，相同的 6 天培养表明，与对照组相比，IL-7（而不是 TSLP）显著降低了凋亡 CD4(+)T 细胞的频率。更重要的是，将 6 天启动的 OT-II T 细胞过继转移到 CD45.1(+)同基因小鼠中表明，与对照组相比，IL-7（而不是 TSLP）分别将转移的 CD4(+)T 细胞数量提高了 3 倍和 4 倍，分别在脾脏（p<0.05）和淋巴结（p<0.05）中。几乎所有转移的 CD4(+)T 细胞群体都表现出效应（CD44(+)CD62L(-)）或中央（CD44(+)CD62L(+)）记忆 T 细胞的表型。因此，我们得出结论，在启动时暴露于 IL-7 会增加 CD4(+)记忆 T 细胞的频率。
