Carbonari M, Cherchi M, Paganelli R, Giannini G, Galli E, Gaetano C, Papetti C, Fiorilli M
Department of Clinical Immunology, University of Rome, La Sapienza, Italy.
N Engl J Med. 1990 Jan 11;322(2):73-6. doi: 10.1056/NEJM199001113220201.
In ataxia-telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: alpha/beta chains on mature cells and gamma/delta chains mostly on immature cells. We studied 10 patients with ataxia-telangiectasia and found that most had a relative increase of circulating T cells bearing gamma/delta receptors rather than alpha/beta receptors, as compared with normal subjects (P less than 0.001). Patients with other immune deficits, including eight with common variable immunodeficiency, one with Wiskott-Aldrich syndrome, two with hyperimmunoglobulinemia E syndrome, and one with severe combined immunodeficiency, had normal ratios of gamma/delta-bearing to alpha/beta-bearing cells. A marked predominance of gamma/delta-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in gamma/delta-bearing T cells in the patients with ataxia-telangiectasia was largely accounted for by cells that reacted with the monoclonal antibody BB3, an apparently distinct subset of T cells that selectively express the C gamma 1 gene product of the T-cell receptor. Although they had normal ratios of gamma/delta-bearing to alpha/beta-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing C gamma 2 that reacted with the monoclonal antibody delta-TCS-1. We conclude that the increased ratio of gamma/delta-bearing to alpha/beta-bearing T cells in ataxia-telangiectasia may reflect both a recombinational defect that interferes with T-cell and B-cell gene rearrangements and an inability to repair damage to the DNA.
在共济失调毛细血管扩张症中，B细胞和T细胞缺陷被认为是由于免疫球蛋白和T细胞受体基因重排缺陷所致。T细胞通过两种与CD3相关的受体识别抗原：成熟细胞上的α/β链和主要在未成熟细胞上的γ/δ链。我们研究了10例共济失调毛细血管扩张症患者，发现与正常受试者相比，大多数患者循环中带有γ/δ受体而非α/β受体的T细胞相对增加（P<0.001）。其他免疫缺陷患者，包括8例常见可变免疫缺陷患者、1例维斯科特-奥尔德里奇综合征患者、2例高免疫球蛋白E综合征患者和1例严重联合免疫缺陷患者，其带有γ/δ的细胞与带有α/β的细胞比例正常。在一名原发性T细胞缺陷患者中发现了明显以带有γ/δ的T细胞为主。共济失调毛细血管扩张症患者中带有γ/δ的T细胞相对增加，很大程度上是由与单克隆抗体BB3反应的细胞所致，BB3是T细胞的一个明显不同的亚群，可选择性表达T细胞受体的Cγ1基因产物。尽管常见可变免疫缺陷患者带有γ/δ的T细胞与带有α/β的T细胞比例正常，但与单克隆抗体δ-TCS-1反应的表达Cγ2的T细胞数量显著增加（P = 0.01）。我们得出结论，共济失调毛细血管扩张症中带有γ/δ的T细胞与带有α/β的T细胞比例增加，可能既反映了干扰T细胞和B细胞基因重排的重组缺陷，也反映了无法修复DNA损伤的情况。
