Lack of specific antibody response in common variable immunodeficiency (CVID) associated with failure in production of antigen-specific memory T cells
Lack of specific antibody response in common variable immunodeficiency (CVID) associated with failure in production of antigen-specific memory T cells
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DOI：
10.1046/j.1365-2249.1997.d01-993.x
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发表时间：
1997-04-01
影响因子：
4.6
通讯作者：
Farrant, J
中科院分区：
文献类型：
--
作者：
Kondratenko, I;Amlot, PL;Farrant, J
在抗体缺乏病CVID中已经描述了几种T细胞缺陷，但是关于特异性T细胞群体对初级新抗原的应答的产生的数据很少。我们现在已经使用新抗原，钥孔血蓝蛋白（KLH）和DNP-Ficoll的免疫接种，以评估CVID患者和正常供体的免疫应答。免疫后2周和4周检查B和T细胞应答。通过ELISA检查血清中的IgM和IgG抗KLH反应，并通过血凝检查血清中的抗DNP-Ficoll活性。通过有限稀释培养系统中的DNA合成来测量KLH应答性T细胞的频率。用KLH脉冲富集树突状细胞的低密度细胞，并与不同数量的自体T细胞一起培养。来自正常供体和患者的T细胞显示抗原特异性前体T细胞的低频率（小于或等于1：200 000）。KLH免疫后，正常供体的频率增加（2周和4周分别为1：60 000和1：30 000），而CVID患者的频率与免疫前水平相比没有变化。该缺陷可能扩展到抗原特异性细胞的功能障碍，而不仅仅是由于细胞数量减少，因为“阳性”威尔斯孔的平均响应也减少。血清特异性抗体反应与T细胞数据平行，因为所有正常供体但没有CVID患者产生IgG KLH特异性抗体。CVID患者确实产生了针对T-非依赖性DNP-Ficoll的IgM抗体，但水平低于正常对照。这些数据表明，CVID患者的T和B细胞对特异性抗原的反应都有缺陷，表明两种谱系都存在抗体缺陷。
Several T cell defects have been described in the antibody deficiency disease, CVID, but there have been few data on the generation of responses of specific T cell populations to primary neoantigens. We have now used immunization with the neoantigens, keyhole limpet haemocyanin (KLH) and DNP-Ficoll, to evaluate immune responses in CVID patients and normal donors. B and T cell responses were examined 2 and 4 weeks post-immunization. Sera were examined for IgM and IgG anti-KLH responses by ELISA and for anti-DNP-Ficoll activity by haemagglutination. The frequency of KLH-responsive T cells was measured by DNA synthesis in a limiting dilution culture system. Low density cells enriched for dendritic cells were pulsed with KLH and cultured with different numbers of autologous T cells. T cells from normal donors and from patients showed a low frequency of antigen-specific precursor T cells (less than or equal to 1:200 000). After KLH immunization the frequency increased in normal donors (1:60 000 and 1:30 000 at 2 and 4 weeks, respectively), while in CVID patients it did not change from the preimmunization level. The defect may extend to a dysfunction of antigen-specific cells, rather than being solely due to the reduced numbers of cells, since mean responses of 'positive' wells were also reduced. The serum-specific antibody response paralleled the T cell data, in that all normal donors but none of the CVID patients generated IgG KLH-specific antibodies. CVID patients did produce IgM antibodies against the T-independent DNP-Ficoll, but at a lower level than normal controls. These data show that both T and B cells from CVID patients have defective responses to specific antigen, implicating both lineages in the antibody deficiency.