Prevention of Th2-mediated murine allergic airways disease by soluble antigen administration in the neonate

It has been demonstrated recently that neonatal antigen administration in the mouse can lead to priming for Th2-mediated immune responses. This observation has important implications for the development of vaccination strategies in humans, particularly for individuals who may be predisposed to atopy or asthma. In this paper it is shown that although i.p. administration of antigen (100 μg) in adjuvant to the neonate does indeed prime for Th2-mediated disease in mice [allergic airways disease (AAD)], when the same relatively low dose of antigen is given in soluble form no priming occurs. Further, administration of a larger dose of soluble antigen (1 mg) actually prevents the ability to prime for a Th2 response subsequently and so prevents the induction of AAD. Protection from disease was associated with evidence of functional inactivation of both Th1 and Th2 ovalbumin-specific T cells. In contrast, administration of a very low dose of antigen (10 μg) primed for a Th2 response in a similar fashion to antigen in adjuvant. We suggest that the adjuvant lowers the “effective” dose of antigen administered in the neonate and thereby primes for Th2-type immune responses. These findings demonstrate that neonatal antigen administration can inhibit Th2-mediated diseases, such as AAD, but the dose of antigen may be critical to avoid predisposition to disease.

近期已有研究证实，在小鼠模型中对新生个体实施抗原免疫，可引发Th2介导的免疫应答致敏。这一发现对于人类疫苗接种策略的研发具有重要指导意义，尤其针对那些特应性体质或哮喘易感人群。本研究表明：尽管对新生小鼠腹腔内（intraperitoneal, i.p.）注射佐剂包裹的100μg抗原，确实可使其罹患Th2介导的疾病——气道变应性疾病（AAD），但以可溶性形式给予同等剂量的抗原时，并不会触发致敏反应。进一步研究发现，给予更高剂量的可溶性抗原（1mg），反而会抑制后续Th2应答的致敏能力，从而阻止气道变应性疾病的诱导发生。这种疾病防护效应，与Th1和Th2型卵清蛋白特异性T细胞的功能失活现象密切相关。与之相反，给予极低剂量的抗原（10μg），则可通过与佐剂包裹抗原相似的方式触发Th2应答致敏。我们推测，佐剂可降低新生小鼠免疫时的抗原"有效"剂量，进而介导Th2型免疫应答的致敏。本研究结果表明，新生期抗原免疫可抑制Th2介导的疾病（如气道变应性疾病），但抗原剂量是避免诱发疾病易感性的关键因素。