Inhibition of myeloid dendritic cell accessory cell function and induction of T cell anergy by alcohol correlates with decreased IL-12 production
Inhibition of myeloid dendritic cell accessory cell function and induction of T cell anergy by alcohol correlates with decreased IL-12 production
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DOI：
10.4049/jimmunol.173.5.3398
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Szabo, G
中科院分区：
文献类型：
--
作者：
Mandrekar, P;Catalano, D;Szabo, G
酒精消耗抑制辅助细胞功能和ag特异性T细胞反应。骨髓树突状细胞（DCs）协调先天免疫反应和T细胞活化。在本报告中，我们发现正常志愿者体内适量饮酒（0.8 g/kg体重）可抑制DC异刺激能力。此外，在DC分化过程中，体外酒精处理显著降低了使用初始CD4(+) T细胞的MLR的异源刺激活性，并抑制了DC的破伤风类毒素银呈递。酒精处理的树突状细胞显示IL-12减少，IL-10产生增加，共刺激分子CD80和CD86表达减少。在MLR期间，外源性IL-12和IL-2的加入，而不是IL-10的中和，改善了酒精处理的dc的异源刺激能力。初始CD4(+) T细胞用酒精处理的dc，显示ifn - γ产生减少，外源性IL-12恢复，表明抑制Th1反应。此外，用酒精处理的dc诱导的CD4(+) T细胞对同样供体来源的正常dc的后续刺激反应较低，这表明酒精处理的dc诱导T细胞能量的能力。lps诱导的酒精处理的未成熟DC的成熟部分恢复了减少的异刺激活性，而仅在DC成熟期间给予酒精不能抑制DC功能，这表明酒精主要损害DC分化而不是成熟。作为DC成熟标志的NFkappaB激活不受酒精的影响。综上所述，体外和体内的酒精都可以通过抑制DC分化和辅助细胞功能，通过降低IL-12诱导的机制，损害Th1免疫应答的产生。
Alcohol consumption inhibits accessory cell function and Ag-specific T cell responses. Myeloid dendritic cells (DCs) coordinate innate immune responses and T cell activation. In this report, we found that in vivo moderate alcohol intake (0.8 g/kg of body weight) in normal volunteers inhibited DC allostimulatory capacity. Furthermore, in vitro alcohol treatment during DC differentiation significantly reduced allostimulatory activity in a MLR using naive CD4(+) T cells, and inhibited tetanus toxoid Ag presentation by DCs. Alcohol-treated DCs showed reduced IL-12, increased IL-10 production, and a decrease in expression of the costimulatory molecules CD80 and CD86. Addition of exogenous IL-12 and IL-2, but not neutralization of IL-10, during MLR ameliorated the reduced allostimulatory capacity of alcohol-treated DCs. Naive CD4(+) T cells primed with alcohol-treated DCs showed decreased IFN-gamma production that was restored by exogenous IL-12, indicating inhibition of Th1 responses. Furthermore, CD4(+) T cells primed with alcohol-treated DCs were hyporesponsive to subsequent stimulation with the same donor-derived normal DCs, suggesting the ability of alcohol-treated DCs to induce T cell anergy. LPS-induced maturation of alcohol-treated immature DCs partially restored the reduced allostimulatory activity, whereas alcohol given only during DC maturation failed to inhibit DC functions, suggesting that alcohol primarily impairs DC differentiation rather than maturation. NFkappaB activation, a marker of DC maturation was not affected by alcohol. Taken together, alcohol both in vitro and in vivo can impair generation of Th1 immune responses via inhibition of DC differentiation and accessory cell function through mechanisms that involve decreased IL-12 induction.