Department of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080, PR China.
Immunobiology. 2011 Apr;216(4):477-84. doi: 10.1016/j.imbio.2010.09.003. Epub 2010 Sep 17.
Most of the studies evaluating the function of tuberculosis (TB)-specific T cells were only based on the ability to produce cytokines, which may not fully reflect the function of T cells. In the present study, we confirmed that Bacille Calmette Guerin (BCG) could significantly induce cytokine production by CD4(+) T cells from BCG-vaccinated PPD(+) donors. In addition, CD4(+) T cells were activated, divided and proliferated in response to BCG stimulation. Phenotypic analysis showed that IFN-γ(+)CD4(+) T cells displayed CD45RA(-)CCR7(+/-)CD62L(-), indicating that these CD4(+) T cells were central and effector memory cells. The analysis of cytokine profiles demonstrated that most of BCG-specific BrdU(+)CD4(+) T cells produced Th1 cytokines in response to polyclonal stimulation. In addition, we found that regulatory T cells (Treg) suppressed BCG-induced proliferation and IFN-γ production by memory CD4(+) T cells. The suppressive effects of Treg on BCG-specific responses of CD4(+) T cells could be partially reversed by blocking the production of IL-10. Taken together, our results demonstrated that functional central and effector memory BCG-specific CD4(+) T cells could be detected based on the activation, proliferation and division of these cells, and modulated by Treg in PBMCs from BCG-vaccinated PPD(+) donors.
大多数评估结核分枝杆菌（TB）特异性 T 细胞功能的研究仅基于产生细胞因子的能力，这可能不能完全反映 T 细胞的功能。在本研究中，我们证实卡介苗（BCG）可显著诱导 BCG 疫苗接种的 PPD（+）供体的 CD4（+）T 细胞产生细胞因子。此外，CD4（+）T 细胞在受到 BCG 刺激后被激活、分裂和增殖。表型分析显示，IFN-γ（+）CD4（+）T 细胞表达 CD45RA（-）CCR7（+/-）CD62L（-），表明这些 CD4（+）T 细胞为中央和效应记忆细胞。细胞因子谱分析表明，大多数 BCG 特异性 BrdU（+）CD4（+）T 细胞在受到多克隆刺激时产生 Th1 细胞因子。此外，我们发现调节性 T 细胞（Treg）抑制记忆 CD4（+）T 细胞的 BCG 诱导增殖和 IFN-γ产生。通过阻断 IL-10 的产生，可部分逆转 Treg 对 CD4（+）T 细胞对 BCG 特异性反应的抑制作用。总之，我们的结果表明，可基于这些细胞的激活、增殖和分裂，从 BCG 疫苗接种的 PPD（+）供体的 PBMC 中检测到功能性中央和效应记忆 BCG 特异性 CD4（+）T 细胞，并且可被 Treg 调节。
