DECREASED CELL-MEDIATED-IMMUNITY IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS
DECREASED CELL-MEDIATED-IMMUNITY IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1016/0168-8227(95)00168-8
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发表时间：
1995-05-01
影响因子：
5.1
通讯作者：
SHAIO, MF
中科院分区：
文献类型：
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作者：
CHANG, FY;SHAIO, MF
非胰岛素依赖型糖尿病(NIDDM)患者外周血单个核细胞对植物血凝素(PHA)和其他有丝分裂原的增殖反应减弱。本研究旨在确定淋巴细胞增殖减少是否由细胞因子的产生减少或白细胞介素2受体(IL-2R)的表达减少所致。NIDDM患者(n=34)和健康对照组(n=22)的单个核细胞在含有PHA、刀豆蛋白-A和佛波酯的RPMI-1640培养液中培养。NIDDM患者的[H-3]胸腺嘧啶核苷摄取减少(57%，P<0.01)，IL-2R阳性细胞百分比减少(61%，P<0.05)，肿瘤坏死因子-α水平升高(200%，P<0.05)。NIDDM患者补体受体(CR)3阳性单核细胞百分比也降低(为对照组的72%，P<0.05)。而IL-1β、IL-2和干扰素-γ的产生、PAN T细胞(CD3)、T辅助细胞(CD_4)、T抑制细胞(CD_8)的百分率、CD_4/CD_8比值以及免疫球蛋白G的CRI和Fc受体(Fc-Gamma RII和Fc-Gamma RIII)的表达在NIDDM患者和健康人之间均无显著差异。人重组IL-2不能恢复PHA刺激的NIDDM患者单个核细胞对[H-3]胸腺嘧啶核苷的摄取。当培养液中葡萄糖浓度增加到27.8 mmol/l时，并不抑制正常人活化的淋巴细胞摄取[H-3]胸腺嘧啶核苷和表达IL-2R。活化淋巴细胞上IL-2R表达降低可能是NIDDM患者淋巴细胞增殖不足的原因之一。提示NIDDM患者单核细胞CR3表达减少，淋巴细胞增殖减少，IL-2R表达减少，而产生更多的肿瘤坏死因子-α，可能是细胞免疫功能受损的原因。
Peripheral blood mononuclear cells from patients with non-insulin-dependent diabetes mellitus (NIDDM) show reduced proliferative response to phytohemagglutinin (PHA) and other mitogens. This study was undertaken to determine whether this reduced lymphocyte proliferation is mediated by a decreased production of cytokine or decreased expression of interleukin-2 receptor (IL-2R). Mononuclear cells from NIDDM patients (n = 34) and healthy controls (n = 22) were cultured in RPMI-1640 media containing PHA, concanavalin-A and phorbol myristate acetate. NIDDM patients showed reduced [H-3]thymidine uptake (57% of controls, P < 0.01), reduced percentage of IL-2R-positive cells (61% of controls, P < 0.02) and increased level of tumor necrosis factor (TNF)-alpha(200% of controls, P < 0.05). The percentage of complement receptor (CR) 3-positive monocytes from NIDDM patients was also decreased (72% of controls, P < 0.05). However, the production of IL-1 beta, IL-2 and interferon-gamma, the percentages of pan T cells (CD3), T helper cells (CD4), T suppressor cells (CD8), the ratio of CD4/CD8 and the expression of CRI and Fc receptors for immunoglobulin G (Fc gamma RII and Fc gamma RIII) were not significantly different between NIDDM patients and healthy subjects. Human recombinant IL-2 was unable to restore the [H-3]thymidine uptake by PHA-stimulated mononuclear cells from NIDDM patients. Elevation of glucose concentration up to 27.8 mmol/1 in the culture medium did not suppress the [H-3]thymidine uptake and IL-2R expression by activated lymphocytes from healthy subjects. The decreased expression of IL-2R on activated lymphocytes might be responsible for the insufficient lymphocyte proliferation in NIDDM patients. These findings suggest that decreased expression of CR3 on monocytes, decreased lymphocyte proliferation and decreased IL-2R expression despite a higher production of TNF-alpha may explain the impaired cell-mediated immunity seen in NIDDM patients.