吲哚胺2,3双加氧酶对小鼠CD4+T细胞增殖的抑制作用

目的 探讨吲哚胺2,3双加氧酶(IDO)抑制T细胞增殖的机制。方法 通过低色氨酸(10μmol/L)培养基(LTM)和/或添加不同浓度(50、100、200和400μmol/L)色氨酸代谢产物(TC),观察小鼠树突细胞(DC)与异系CD4+T细胞培养体系中后者的增殖。Annexin-V及碘化丙锭(PI)双染法测定CD4+T细胞凋亡。结果 LTM中CD4+T细胞增殖指数(2.718 ±0.010)及抑制CD4+T细胞增殖的TC浓度(200μmol/L KYN或50 μmol/L 3-HAA)较正常色氨酸培养基(NTM)(3.385 ±0.013,400 μmol/L KYN或100 μmol/L 3-HAA)显著降低,差异有统计学意义(P＜0.01)。LTM中CD4+T细胞早期凋亡率(33.163±0.556)％显著高于NTM(8.867 ±0.565)％ (P ＜0.01)。NTM中CD4+T细胞凋亡率随3-HAA浓度升高而增加[3-HAA浓度50、100、200和400 μmol/L组中分别为(14.433 ±0.640)％、(22.273±0.629)％、(37.363±0.953)％和(46.643±0.633)％]。结论 LTM及TC均可通过诱导凋亡来抑制CD4+T细胞增殖,两者具有叠加效应。

Inhibitory effect of indoleamine 2,3-dioxygenase on proliferation of CD4 + T lymphocytes

Objective To reveal the mechanism of inhibitory effect on CD4 + T lymphocytes proliferation by indoleamine 2,3-Dioxygenase (IDO). Methods Low-Tryptophan medium ( 10 μmol/L) and/or Tryptophan catabolites (50, 100,200 and 400 μmoL/L) were used to observe CD4 + T lymphocytes proliferation in a mixed culturing system with murine dentritic cells (DC) and allogeneic CD4 + T lymphocytes in vitro. Annexin-V and PI double staining method was used to determine CD4 +T lymphocytes apoptosis.Results Stimulation index in low-Tryptophan medium group (2. 718 ±0. 010) was decreased significantly (P ＜0. 01 ) as compared with that in normal Tryptophan medium group (3. 385 ±0. 013). The inhibitory concentrations of Tryptophan catabolites in low-Trptophan medium group (200 μmol/L KYN or 50 μmol/L 3-HAA) were lower significantly than those in nomal Trptophan medium group (400 μmol/L KYN or 100 μmol/L 3-HAA). Apoptosis rate of CD4+T cells in low-tryptophan medium goup (33. 163 ± 0. 556)％ was significantly higher (P ＜ 0. 01 ) than that in the control group (8. 867 ± 0. 565 )％. The apoptosis rate was increased with the increase in concentrations of Tryptophan catabolites[(14.433 ± 0. 640 )％,(22.273 ±0.629)％, (37.363 ±0.953)％ and (46.643 ±0.633)％ in the medium of 50, 100, 200 and 400 μmol/L of 3-HAA]. Conclusion Low-tryptophan medium and tryptophan catabontes both can inhibit the proliferation of CD4 + T lymphocytes by inducing apoptosis.