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

Abstract

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. Key words: Indoleamine 2,3-Dioxygenase; Tryptophan; Dendritic cells ; Apoptosis