Poulter L W, Burke C M
Department of Clinical Immunology, Royal Free Hospital, London, U.K.
Immunobiology. 1996 Oct;195(4-5):574-87. doi: 10.1016/S0171-2985(96)80023-4.
Allergic lung diseases such as atopic asthma and extrinsic allergic alveolitis are now recognized as chronic inflammatory lung diseases promoted by dysregulation of T cell-mediated immune mechanisms. The basis of this regulation and the impact of the atopic status of these individuals on this chronic inflammatory disease have yet to be fully explained. The studies described in this paper reveal mechanisms of macrophage lymphocyte interaction in which evidence is presented that a balance of functionally distinct macrophage subsets needs to be maintained to regulate T cell reactivity in the lung. Similarly a balance within the T cell populations may influence and regulate the relative proportions of functionally distinct macrophages. Investigations of bronchoalveolar lavage and biopsy from patients with allergic lung disease have revealed a gross imbalance within the lung macrophage populations and an associated dysregulation in T cell stimulation. In vitro studies have revealed that imbalances in the macrophage populations may lead to changes in local level of cytokine production specifically TGF-beta which would then impact on the control of T cell populations. Conversely aberrant development of activated T cells with a TH2-like cytokine repertoire may influence the balance of macrophages. Our in vitro studies have revealed that macrophage phenotype and function can be modulated in vitro by contact with T cell-derived cytokines and that this change in phenotype is reflected in a change in function. These data support the hypothesis that components of the immune system normally associated with allergic reactions may be stimulated in the absence of any overt atopic reactivity in the individual concerned. Thus immediate type allergic reactions may represent a "super-imposed" burden [provocating factor] in atopic individuals but the underlying immunopathogenesis of these diseases may not be dependent on this state of immediate type hypersensitivity. It is concluded that the loss of balance within functional distinct macrophage populations within the lung may represent the fundamental problem in allergic lung disease. This possibility is discussed in the light of other work in this field.
过敏性肺部疾病，如特应性哮喘和外源性过敏性肺泡炎，现在被认为是由T细胞介导的免疫机制失调所引发的慢性炎症性肺部疾病。这种调节的基础以及这些个体的特应性状态对这种慢性炎症性疾病的影响尚未得到充分解释。本文所述的研究揭示了巨噬细胞与淋巴细胞相互作用的机制，其中有证据表明，需要维持功能不同的巨噬细胞亚群之间的平衡，以调节肺部的T细胞反应性。同样，T细胞群体内部的平衡可能会影响和调节功能不同的巨噬细胞的相对比例。对过敏性肺部疾病患者的支气管肺泡灌洗和活检研究表明，肺部巨噬细胞群体存在严重失衡，并且T细胞刺激也存在相关失调。体外研究表明，巨噬细胞群体的失衡可能导致细胞因子产生的局部水平发生变化，特别是转化生长因子-β，这进而会影响T细胞群体的控制。相反，具有TH2样细胞因子谱的活化T细胞的异常发育可能会影响巨噬细胞的平衡。我们的体外研究表明，巨噬细胞的表型和功能可以通过与T细胞衍生的细胞因子接触在体外进行调节，并且这种表型变化反映在功能变化上。这些数据支持这样一种假设，即在相关个体没有任何明显特应性反应的情况下，通常与过敏反应相关的免疫系统成分可能会被激活。因此，速发型过敏反应可能代表特应性个体中的一种“叠加”负担[激发因素]，但这些疾病的潜在免疫发病机制可能不依赖于这种速发型超敏反应状态。得出的结论是，肺部功能不同的巨噬细胞群体之间平衡的丧失可能是过敏性肺部疾病的根本问题。结合该领域的其他研究对这种可能性进行了讨论。
