Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy.
Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy.
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尼古丁对免疫反应的影响。
DOI：
10.4049/jimmunol.156.7.2384
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发表时间：
1996
影响因子：
4.4
通讯作者：
M. Sopori
中科院分区：
文献类型：
--
作者：
Yuemei Geng;S. M. Savage;S. Razani;M. Sopori
以前，我们已经表明，长期尼古丁治疗（NT）动物的T和B淋巴细胞表现出对Ag（Ag受体连接）激活的耐受性，如它们动员细胞内钙的能力降低所示，至少在T细胞中，细胞停滞在细胞周期的G 0/G1期。在此，我们证明了NT T细胞显著丧失了上调三磷酸肌醇合成的能力，以响应TCR连接或AIF-4对G蛋白的非特异性激活。然而，增加cAMP浓度的T细胞激活G蛋白敏感的腺苷酸环化酶的霍乱或百日咳毒素没有显着影响尼古丁治疗。有趣的是，与对照T细胞相比，NT T细胞中三磷酸肌醇的背景水平显著升高，表明这些细胞中存在一定程度的活化。这一推论进一步得到了观察结果的支持，即来自NT动物的幼稚T细胞表现出几种底物的酪氨酸磷酸化，包括磷脂酶C-γ 1，其在未刺激的对照T细胞中不存在或磷酸化不足。此外，当4周尼古丁治疗后，尼古丁泵被删除，血清可替宁水平下降到背景，抑制抗体形成细胞和钙离子反应持续至少2周以上。这些结果表明，慢性体内尼古丁暴露导致T细胞无反应性，并可能有助于尼古丁/香烟烟雾诱导的免疫抑制。
Previously, we have shown that both T and B lymphocytes from chronically nicotine-treated (NT) animals exhibit tolerance to activation by Ags (ligation of Ag receptors), as indicated by their decreased ability to mobilize intracellular calcium and, at least in T cells, arrest of cells in the G0/G1 phase of the cell cycle. Herein, we demonstrate that NT T cells significantly lose their ability to up-regulate inositol trisphosphate synthesis in response to TCR ligation or nonspecific activation of G proteins by AIF-4. However, increases in cAMP concentrations of T cells following activation of G protein-sensitive adenylate cyclase by cholera or pertussis toxin were not significantly affected by the nicotine treatment. Interestingly, compared with control T cells, the background levels of inositol trisphosphate were significantly elevated in NT T cells, indicating some degree of activation in these cells. This inference was further supported by observations that naive T cells from NT animals exhibit tyrosine phosphorylation of several substrates, including phospholipase C-gamma1, which were either absent or underphosphorylated in unstimulated control T cells. Moreover, when, after 4-wk nicotine treatment, nicotine pumps were removed and serum cotinine levels fell to background, inhibition of the Ab-forming cells and Ca2+ responses continued for at least 2 more wk. These results suggest that chronic in vivo nicotine exposure leads to T cell anergy and may contribute to nicotine/cigarette smoke-induced immunosuppression.