Ozawa H, Nakagawa S, Tagami H, Aiba S
Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.
J Invest Dermatol. 1996 Mar;106(3):441-5. doi: 10.1111/1523-1747.ep12343589.
It has been reported that the in vivo maturation of Langerhans cells after hapten painting is mediated by IL-1 beta while Langerhans cell maturation after in vitro culture is mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). To clarify the reason for this discrepancy, we examine the expression of Ia antigen and several co-stimulatory molecules on Langerhans cells that were activated by in vitro culture, by hapten painting, or by an intradermal injection of several cytokines. Both cultured Langerhans cells and those activated by hapten painting increased the expression of Ia antigen and all the co-stimulatory molecules (i.e., intercellular adhesion molecule-1 [ICAM-1], B7-1, B7-2, and CD40). In contrast, an intradermal injection of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) increased the expression of Ia antigen, ICAM-1, B7-2, and CD40, but not that of B7-1. These data indicate that IL-1 beta or TNF-alpha is not sufficient to induce B7-1 expression on Langerhans cells in vivo. Subsequently we examined the effect of anti-cytokine antibodies (Abs) on the expression of those molecules on cultured Langerhans cells. While none of the Abs to IL-1 beta, TNF-alpha, or GM-CSF changed the upregulation of Ia antigen, ICAM-1, or CD40 on cultured Langerhans cells, anti-GM-CSF Ab suppressed that of B7-1 and B7-2. Taken together, our present results suggest that IL-1 beta is required for the upregulation of Ia, ICAM-1, B7-2, and CD40, while GM-CSF is required for the upregulation of B7-1 and B7-2, although it still remains unclear why the injected GM-CSF could not augment B7-1 expression on Langerhans cells in vivo and why anti-IL-1 beta Ab did not suppress the upregulation of Ia, ICAM-1, or CD40 on cultured Langerhans cells.
据报道，半抗原涂抹后朗格汉斯细胞在体内的成熟由白细胞介素-1β（IL-1β）介导，而体外培养后朗格汉斯细胞的成熟由粒细胞-巨噬细胞集落刺激因子（GM-CSF）介导。为了阐明这种差异的原因，我们检测了经体外培养、半抗原涂抹或皮内注射几种细胞因子激活的朗格汉斯细胞上Ia抗原和几种共刺激分子的表达。培养的朗格汉斯细胞和经半抗原涂抹激活的朗格汉斯细胞均增加了Ia抗原和所有共刺激分子（即细胞间黏附分子-1[ICAM-1]、B7-1、B7-2和CD40）的表达。相比之下，皮内注射白细胞介素-1β（IL-1β）或肿瘤坏死因子-α（TNF-α）增加了Ia抗原、ICAM-1、B7-2和CD40的表达，但未增加B7-1的表达。这些数据表明，IL-1β或TNF-α不足以在体内诱导朗格汉斯细胞上B7-1的表达。随后，我们检测了抗细胞因子抗体（Abs）对培养的朗格汉斯细胞上这些分子表达的影响。虽然针对IL-1β、TNF-α或GM-CSF的抗体均未改变培养的朗格汉斯细胞上Ia抗原、ICAM-1或CD40的上调，但抗GM-CSF抗体抑制了B7-1和B7-2的上调。综上所述，我们目前的结果表明，IL-1β是Ia、ICAM-1、B7-2和CD40上调所必需的，而GM-CSF是B7-1和B7-2上调所必需的，尽管目前尚不清楚为什么注射的GM-CSF不能增强体内朗格汉斯细胞上B7-1的表达，以及为什么抗IL-1β抗体不能抑制培养的朗格汉斯细胞上Ia、ICAM-1或CD40的上调。
