Leonard W J, Noguchi M, Russell S M, McBride O W
Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Immunol Rev. 1994 Apr;138:61-86. doi: 10.1111/j.1600-065x.1994.tb00847.x.
X-linked severe combined immunodeficiency is characterized by severe and persistent infections from early life resulting from profound impairment of both cellular and humoral immune function. XSCID is characterized by an absence or diminished number of T cells and histologic evidence of hypoplastic and abnormal differention of the thymic epithelium. The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes. This led to the speculation that IL-2R gamma would prove to be a common gamma chain, gamma c, which would play important roles in other cytokine receptors in addition to the IL-2 receptor. There is now compelling evidence to support a role in at least two other cytokine receptors, namely the IL-4 and IL-7 receptors. Thus, with inactivation of gamma c, multiple cytokine systems are simultaneously affected, resulting in the profoundly impaired phenotype of XSCID. It is possible and even likely that gamma c will be found to be a functional component of additional receptors as well. These findings have resulted in a significant improvement in our understanding of the pathophysiologic development of the defects in XSCID and also have important ramifications for prenatal and postnatal diagnosis, carrier female identification, and gene therapy for XSCID.
X连锁重症联合免疫缺陷病的特征是自幼年起就出现严重且持续的感染，这是由于细胞免疫和体液免疫功能严重受损所致。XSCID的特征是T细胞数量缺失或减少，以及胸腺上皮发育不全和分化异常的组织学证据。发现这种疾病是由IL-2Rγ链突变引起的，这令人惊讶，因为IL-2缺陷小鼠和人类SCID患者的表型较轻。这引发了一种推测，即IL-2Rγ将被证明是一种共同的γ链，γc，它除了在IL-2受体中发挥作用外，还将在其他细胞因子受体中发挥重要作用。现在有令人信服的证据支持它在至少另外两种细胞因子受体，即IL-4和IL-7受体中发挥作用。因此，随着γc的失活，多个细胞因子系统同时受到影响，导致XSCID出现严重受损的表型。甚至有可能发现γc也是其他受体的功能成分。这些发现显著增进了我们对XSCID缺陷病理生理发展的理解，也对XSCID的产前和产后诊断、携带者女性鉴定以及基因治疗具有重要意义。
