关键词: 结核/免疫学, T淋巴细胞亚群, 色氨酸, 犬尿氨酸

Abstract: Objective  To identify the association between the changes of tryptophan (TRP) metabolites and the imbalance of the T-cell subsets in patients with tuberculosis (TB) and to explore the possible mechanism. Methods  The TB patients enrolled in this study came from Beijing Chest Hospital. Forty-five patients were randomly selected from 104 TB patients who were diagnosed in the hospital from September 2012 to December 2012 (patients with complications, such as diabetes, were excluded). At the same time, 39 healthy controlled subjects were randomly recruited from 100 volunteers who received physical examinations at Changping District TB Dispensary of Beijing. The proportions of regulatory T (Treg) cells and T helper 17 (Th17) cells in peripheral blood of enrolled TB patients and healthy subjects were tested by flow cytometry assay. By addng TRP and its metabolites (KYN and QA) to stimulate CD4⁺ and CD8⁺ T lymphocytes in vitro, their effects on cell apoptosis and proliferation were analyzed. SPSS 17.0 was used for statistic analysis. The results of the tests were presented as “x±s” and P<0.05 of t-test was regarded as statistical significance.  Results  To compare with the healthy control group, the proportion of the Treg cells in TB patients significantly increased ((1.49±0.82)% in TB group and(0.41±0.26)% in control group; t=33.64, P=0.000), and the proportion of Th17 in TB patients increased too ((1.04±0.72)% in TB group and (0.73±0.43)% in control group), but it was not significant difference (t=44.46, P=0.071). The results of stimulation tests in vitro showed that: high concentration of KYN (2.0 mmol/L) induced the apoptosis of CD4⁺ T cells ((8.40±3.28)% in healthy control group and (30.07±7.37)% in TB group; t=7.49, P=0.000) and CD8⁺ T cells ((15.31±1.88)% in control group and (26.36±1.09)% in TB group; t=4.89, P=0.003). However, after stimulated with a high concentration of TRP (2.0 mmol/L) or QA (2.0 mmol/L) for 24 hours, the proportions of apoptosis of the CD4⁺ T cells in TB group were (6.66±0.96)% and (6.85±0.43)% respectively, which slightly decreased comparing with the proportions in control group ((8.40±3.28)% and (8.40±3.28)%). The difference was not significant (t=6.42, P=0.189 and t=8.21，P=0.107); the proportions of apoptosis of the CD8⁺ T cells in TB patients were (16.48±4.75)% and (17.18±2.07)% respectively after stimulated with high concentration of TRP (2.0 mmol/L) or QA (2.0 mmol/L), which increased comparing with the proportions in control group ((15.31±1.88)% and (15.31±1.88)%). There was no significant difference between two groups (t=7.41, P=0.238 or t=8.02, P=0.121).  Conclusion  The amount of Treg cells significantly increased in the blood of TB patients. KYN may contribute to the differentiation of T cells by influencing apoptosis of CD4⁺ T cells and CD8⁺ T cells.

Key words: Tuberculosis/immunology, T-lymphocyte subsets, Tryptophan, Kynurenine