A DEFECT IN THE EARLY PHASE OF T-CELL RECEPTOR-MEDIATED T-CELL ACTIVATION IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY
A DEFECT IN THE EARLY PHASE OF T-CELL RECEPTOR-MEDIATED T-CELL ACTIVATION IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY
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DOI：
10.1182/blood.v84.12.4234.bloodjournal84124234
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发表时间：
1994-12-15
期刊：
影响因子：
20.3
通讯作者：
EIBL, MM
中科院分区：
文献类型：
--
作者：
FISCHER, MB;HAUBER, I;EIBL, MM
常见变异型免疫缺陷（CVID）的特征是特异性抗体产生受损，所有或选定的IG同种型减少。已经描述了在B细胞、T细胞和抗原呈递细胞水平上的抑制。在本研究中，我们将注意力集中在CVID中的T细胞活化上。24例患者中15例T细胞对回忆抗原（腿、破伤风类毒素、大肠杆菌）无应答。对这15例患者中的11例进行了详细的研究，发现在回忆抗原和超抗原的刺激下，T细胞增殖反应明显降低，白细胞介素2和干扰素γ的产生明显减少（葡萄球菌肠毒素[SEI]）;然而，T细胞对有丝分裂原（抗CD 3单克隆抗体，植物血凝素）的反应正常。破伤风环刺激时白细胞介素-2和干扰素-γ释放的缺陷也可以在患者的纯化CD 4 T细胞中记录，并且存在于高和正常CD 8计数的患者中。此外，患者的T细胞未能响应于超抗原而显著升高细胞内游离钙（Ca++通量），而对佛波醇肉豆蔻酸酯乙酸酯和离子霉素的响应，绕过受体介导的信号传导，未受损。这些结果表明，在CVID患者的一个重要亚组中，触发T细胞受体后，T细胞活化的早期阶段存在缺陷。(C)1994年，美国血液学会。
Common variable immunodeficiency (CVID) is characterized by an impairment of specific antibody production and a decrease in all or selected Ig isotypes. Abnormalities at the level of the B cells, T cells, and antigen-presenting cells have been described. In the present study, we have focused our attention on T-cell activation in CVID. T cells from 15 of 24 patients failed to respond to recall antigens leg, tetanus toxoid, Escherichia coli), Of these 15 patients, 11 were studied in detail and showed significantly decreased T-cell proliferative responses and/or decreased interleukin-2 and interferon-gamma production on T-cell receptor-mediated stimulation with recall antigens and superantigens (staphylococcal enterotoxins [SEI); however, T-cell response to mitogens (anti-CD3 monoclonal antibody, phytohemagglutinin) was normal. The defect in interleukin-2 and interferon-gamma release on tetanus toroid stimulation could also be documented in purified CD4 T cells of the patients and was present in patients with high and normal CD8 counts alike. Furthermore, patients' T cells failed to mount a significant elevation in free intracellular calcium (Ca++ flux) in response to superantigen, whereas the response to phorbol myristate acetate and ionomycin, bypassing receptor-mediated signaling, was unimpaired. These results indicate a defect in the early phase of T-cell activation after triggering of the T-cell receptor in a significant subgroup of CVID patients. (C) 1994 by The American Society of Hematology.