Study on the role of dendritic cells in the atopic dermatitis

特应性皮炎(AD)是一种以Th2为主的炎症性皮肤病，但这种Th1/Th2失衡的机制尚不清楚。我们推测，树突状细胞作为专职的抗原提呈细胞，在决定Th1/Th2平衡中起着重要作用。我们计划研究树突状细胞在AD患者Th1/Th2失衡中的作用。首先，为了了解AD患者T细胞的免疫状态，我们检测了外周血单个核细胞对金黄色葡萄球菌肠毒素B(SEB)的增殖反应，SEB是金黄色葡萄球菌的超抗原之一，与AD的加重有关。我们的研究表明，重度AD患者的T细胞在SEB刺激后容易发生凋亡，不仅Th1，而且Th2活性受到抑制。提示树突状细胞可诱导T细胞凋亡。与这一体外现象相反，我们在伴有葡萄球菌感染的AD病变处观察到很少的凋亡T细胞。为了阐明这一差异，我们假设患者的血清中存在抗细胞凋亡活性。我们检测了AD患者血清是否对T细胞对SEB的应答有影响。结果发现，重症AD患者血清中存在高滴度的抗SEB中和抗体，并显著抑制T细胞对SEB的增殖反应。我们的研究结果表明，抗SEB中和抗体可以拯救T细胞，使其免于凋亡，并反常地下调SEB诱导的炎症反应。

It is known that atopic dermatitis (AD) is a Th2 dominant inflammatory skin disease, however, the mechanism of such Th1/Th2 unbalance is unknown. We hypothesized that dendritic cells, professional antigen presenting cells, have an important role to determine Th1/Th2 balance in this disease. We planed to study the role of dendritic cells on Th1/Th2 unbalance in AD.At first, to investigate the immunological status of T cells in AD patients, we assessed the proliferative response of peripheral blood mononuclear cells to staphylococcal enterotoxin B (SEB), one of the superantigens from S.aureus, which have a role in aggravation of AD.Our studies demonstrated that T cells from the patients with severe AD were prone to undergo apoptosis following SEB stimulation, and that not only Th1 but also Th2 activity was suppressed. Dendritic cells were suggested to induce T cell apoptosis. In contrast to this in vitro phenomenon, we observed few apoptotic T cells at the AD lesion with staphylococcal infection. To clarify this discrepancy, we hypothesized that anti-apoptotic activity was present in the serum of the patient. We examined whether or not sera of AD patients had any influence on T-cell response to SEB.We found that sera from severe AD patients had high titers of anti-SEB neutralizing antibody and markedly suppressed T cell proliferative response to SEB.Our findings suggest that anti-SEB neutralizing antibody may rescue T cells from apoptosis and paradoxically down-regulate inflammatory responses induced by SEB in the patients.