Sotiropoulos Christos, Theodorou George, Repa Constantina, Marinakis Theodoros, Verigou Eugenia, Solomou Elena, Karakantza Marina, Symeonidis Argiris
Hematology Division, Department of Internal Medicine, University of Patras Medical School, Rion of Patras, Greece.
JIMD Rep. 2015;18:107-15. doi: 10.1007/8904_2014_357. Epub 2014 Oct 12.
We investigated peripheral blood T-lymphocyte subpopulations and intracellular expression of IFN-γ, IL-4, IL-10, and IL-13, by whole blood flow cytometry, in 22 type I Gaucher disease (GD) patients. Results were compared with those of 19 sex- and age-matched controls. Patients with GD exhibited decreased frequencies and absolute numbers of CD3+/CD4+ helper T lymphocytes (40.8 ± 9.8% vs. 49.4 ± 5.7%, p = 0.002, and 0.77 ± 0.33 vs. 1.04 ± 0.28 × 10(9)/μL, p = 0.011), as well as increased frequencies of CD3+CD8+ suppressor T lymphocytes (23.8 ± 8.0% vs. 18.4 ± 3.8%, p = 0.010), resulting in a significantly decreased CD4/CD8 cell ratio (p < 0.001). Moreover, they had significantly increased percentages of IFNγ-producing both CD4+ and CD8+ T cells (p = 0.0003 and p = 0.023, respectively), implying a TH-1 polarization pattern. Finally, patients with GD had decreased percentages and absolute numbers of CD4+CD25(dim) T lymphocytes (p = 0.033 and p = 0.007, respectively), of CD4+CD25(high) T lymphocytes (p = 0.039 and p = 0.016, respectively), and of CD4+CD25(high)FOXP3+ regulatory T cells (p = 0.036 and p = 0.019, respectively). Our results demonstrate that patients with GD have a significant numerical impairment of T-helper lymphocytes and a constitutive TH1 direction pattern of activation of both CD4+ and CD8+ cells, associated with a significant decrease of T-regs. Ineffective T-cell control may explain the chronic inflammatory reaction and the increased incidence of lymphoid malignancies, which have been repeatedly reported among patients with GD.
我们采用全血流式细胞术，对22例I型戈谢病（GD）患者的外周血T淋巴细胞亚群以及细胞内干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和白细胞介素-13（IL-13）的表达进行了研究。将结果与19名性别和年龄匹配的对照者进行了比较。GD患者的CD3⁺/CD4⁺辅助性T淋巴细胞频率和绝对数量降低（分别为40.8±9.8%对49.4±5.7%，p = 0.002；以及0.77±0.33对1.04±0.28×10⁹/μL，p = 0.011），同时CD3⁺CD8⁺抑制性T淋巴细胞频率增加（23.8±8.0%对18.4±3.8%，p = 0.010），导致CD4/CD8细胞比值显著降低（p < 0.001）。此外，他们产生IFNγ的CD4⁺和CD8⁺T细胞百分比显著增加（分别为p = 0.0003和p = 0.023），这意味着存在TH-1极化模式。最后，GD患者的CD4⁺CD25（dim）T淋巴细胞百分比和绝对数量降低（分别为p = 0.033和p = 0.007），CD4⁺CD25（high）T淋巴细胞百分比和绝对数量降低（分别为p = 0.039和p = 0.016），以及CD4⁺CD25（high）FOXP3⁺调节性T细胞百分比和绝对数量降低（分别为p = 0.036和p = 0.019）。我们的结果表明，GD患者的辅助性T淋巴细胞存在显著的数量损伤，CD4⁺和CD8⁺细胞的活化呈现出组成性的TH1方向模式，同时调节性T细胞显著减少。无效的T细胞控制可能解释了慢性炎症反应以及GD患者中反复报道的淋巴系统恶性肿瘤发病率增加的现象。
