Hofer M F, Harbeck R J, Schlievert P M, Leung D Y
Department of Pediatrics, The National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
J Invest Dermatol. 1999 Feb;112(2):171-6. doi: 10.1046/j.1523-1747.1999.00492.x.
Microbial agents are known to play a significant role in aggravating allergic diseases. Recently described viral and bacterial superantigens represent one important strategy by which infectious agents can stimulate the immune response. In previous work, we reported that the staphylococcal toxin toxic shock toxin-1 (TSST-1), a prototypic superantigen, induces in vitro total IgE synthesis after cross-linking T and B cells. This study was carried out to establish a potential link between superantigens and the enhanced IgE response to specific allergens in allergic patients. Peripheral blood mononuclear cells from atopic patients were isolated during and outside the pollen allergen season and stimulated with TSST-1, a prototypic superantigen. Total IgE and interferon-gamma production were measured in supernatants of these cultures. Outside the pollen season, TSST-1 significantly increased total IgE production only in the presence of exogenous interleukin-4, whereas during the pollen season IgE production was significantly enhanced without the need of exogenous interleukin-4. This increase in the absence of exogenous interleukin-4 was associated with significantly lower interferon-gamma production by peripheral blood mononuclear cells stimulated by TSST-1 during the pollen season. Moreover, TSST-1 stimulation of peripheral blood mononuclear cells from inhalant allergic patients was followed by an increased production of allergen-specific IgE that was restricted to the allergen to which the patient was allergic and recently exposed. In addition, TSST-1 induced on B cells the expression of B7.2, a molecule that has recently been demonstrated to enhance T helper 2 responses and to be involved in IgE regulation. This study, by demonstrating that superantigens can augment allergen-specific IgE synthesis and B7.2 expression, provides a mechanism by which microbial superantigens may modulate allergic responses.
已知微生物因子在加重过敏性疾病中起重要作用。最近描述的病毒和细菌超抗原代表了感染因子刺激免疫反应的一种重要策略。在先前的研究中，我们报道葡萄球菌毒素中毒性休克毒素-1（TSST-1），一种典型的超抗原，在T细胞和B细胞交联后可诱导体外总IgE合成。本研究旨在建立超抗原与过敏性患者对特定过敏原增强的IgE反应之间的潜在联系。在花粉过敏原季节期间和之外分离特应性患者的外周血单核细胞，并用典型超抗原TSST-1刺激。在这些培养物的上清液中测量总IgE和干扰素γ产生。在花粉季节之外，TSST-1仅在外源性白细胞介素-4存在下显著增加总IgE产生，而在花粉季节期间，无需外源性白细胞介素-4即可显著增强IgE产生。在没有外源性白细胞介素-4的情况下这种增加与花粉季节期间TSST-1刺激的外周血单核细胞产生的干扰素γ显著降低有关。此外，TSST-1刺激吸入性过敏患者的外周血单核细胞后，过敏原特异性IgE的产生增加，且仅限于患者最近接触过的过敏的过敏原。此外，TSST-1诱导B细胞上B7.2分子的表达，最近已证明该分子可增强辅助性T细胞2反应并参与IgE调节。这项研究通过证明超抗原可增强过敏原特异性IgE合成和B7.2表达，提供了一种微生物超抗原可能调节过敏反应的机制。
