alpha-Melanocyte-stimulating hormone induces hapten-specific tolerance in mice.
alpha-Melanocyte-stimulating hormone induces hapten-specific tolerance in mice.
复制标题
α-黑素细胞刺激激素诱导小鼠半抗原特异性耐受。
作者：
Stephan Grabbe;R. Bhardwaj;Karsten Mahnke;M. Simon;Thomas Schwarz;T. Luger
α-黑素细胞刺激激素 (α-MSH) 是一种阿片黑皮质素原衍生肽，具有已知的免疫调节作用，主要通过调节淋巴细胞和单核细胞的细胞因子分泌发挥作用。当应用于表皮时，α-MSH 抑制小鼠接触性超敏反应 (CHS) 反应的诱导和引发。我们质疑全身施用 α-MSH 是否会导致半抗原特异性耐受的诱导。为此，对小鼠进行静脉注射。在致敏（第 0 天）或用半抗原三硝基氯苯 (TNCB) 攻击（第 6 天）前 2 小时，使用 75 微克/千克合成生物活性 α-MSH。致敏前 2 小时或攻击前 2 小时静脉注射 α-MSH 会导致 CHS 反应显着降低。为了区分无反应和耐受，对这些小鼠进行第二次致敏和攻击，但不使用 α-MSH。在第一次致敏前（第 0 天）但在攻击前（第 6 天）未注射 α-MSH 的小鼠，在 10 至 14 天后再次致敏和用相同的 Ag 攻击后也无法产生显着的 CHS 反应。相比之下，这些小鼠对不相关的半抗原二硝基氟苯的敏化未受影响，表明 α-MSH 诱导了半抗原特异性耐受。此外，在重新致敏后5天，从α-MSH处理的小鼠获得的区域淋巴结细胞未能产生响应三硝基苯磺酸（TNCB的水溶性类似物）的IL-2，而来自TNCB致敏的而非α-MSH处理的小鼠以及来自攻击前用α-MSH处理的小鼠的淋巴结细胞在该测定中很容易表现出三硝基苯磺酸特异性IL-2的产生。最后，通过在致敏位点施用抗IL-10 Ab可以消除α-MSH诱导的体内耐受性。这些数据表明，α-MSH 除了对 CHS 的诱导和引发具有抑制作用外，还能够在小鼠中诱导半抗原特异性耐受。因此，α-MSH可能是体内皮肤免疫反应的重要调节介质。
alpha-Melanocyte-stimulating hormone (alpha-MSH) is a proopiomelanocortin-derived peptide with known immunoregulatory effects, acting mainly via modulation of cytokine secretion by lymphocytes and monocytes. When applied epicutaneously, alpha-MSH inhibits both induction as well as elicitation of contact hypersensitivity (CHS) responses in mice. We questioned whether systemically administered alpha-MSH leads to the induction of hapten-specific tolerance. For this purpose, mice were injected i.v. with 75 microgram/kg synthetic bioactive alpha-MSH 2 h before sensitization (day 0) or challenge (day 6) with the hapten, trinitrochlorobenzene (TNCB). Intravenous administration of alpha-MSH 2 h before sensitization or 2 h before challenge resulted in a markedly reduced CHS response. To distinguish between unresponsiveness and tolerance, these mice were sensitized and challenged a second time, but in the absence of alpha-MSH. Mice that had been injected with alpha-MSH before the first sensitization (day 0), but not before challenge (day 6), were also unable to develop a significant CHS response after an additional sensitization and challenge with the same Ag 10 to 14 days later. In contrast, sensitization to the unrelated hapten, dinitrofluorobenzene, was unaffected in these mice, indicating the induction of hapten-specific tolerance by alpha-MSH. Moreover, regional lymph node cells obtained from alpha-MSH-treated mice 5 days after resensitization failed to produce IL-2 in response to trinitrobenzosulfonic acid, the water-soluble analogue of TNCB, whereas lymph node cells from TNCB-sensitized, not alpha-MSH-treated, mice as well as from mice treated with alpha-MSH before challenge readily exhibited trinitrobenzosulfonic acid-specific IL-2 production in this assay. Finally, in vivo tolerance induction by alpha-MSH could be abrogated by the administration of anti-IL-10 Ab at the site of sensitization. These data indicate that alpha-MSH, in addition to its suppressive effect on induction and elicitation of CHS, is able to induce hapten-specific tolerance in mice. Thus, alpha-MSH may be a significant regulatory mediator of cutaneous immune responses in vivo.