Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28
Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28
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DOI：
10.1002/art.1780400508
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发表时间：
1997-05-01
影响因子：
--
通讯作者：
Gray, JD
中科院分区：
文献类型：
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作者：
Horwitz, DA;Tang, FL;Gray, JD
目标。评估系统性红斑狼疮(SLE)患者T细胞对抗CD2单抗(MAb)促有丝分裂反应的能力，并了解该缺陷的分子基础。用抗CD2抗体体外刺激SLE患者和配对对照外周血单个核细胞(PBMC)，并与植物血凝素(PHA)和抗CD3抗体刺激外周血单个核细胞(PBMC)的增殖反应进行比较。用特异性单抗染色后，用流式细胞仪检测淋巴细胞表面标志。在SLE患者中，对抗CD2抗体的增殖反应比抗CD3抗体或PHA抗体的反应降低的程度更大，这一缺陷在接受检查的患者中约有一半被发现，与疾病活动性无关，并经反复检测保持不变。由于抗CD2抗体激活后单核细胞或静止B细胞可以作为T细胞的辅助细胞，我们检测了贴壁细胞被耗尽后的T细胞反应。在大约三分之二的反应减弱、单核细胞耗尽或用来自正常捐赠者的同种异体静息B细胞替代单核细胞的个体中，纠正了缺陷。在PBMC中加入抗CD28抗体，但不加入IL-10中和抗体，在很大程度上逆转了抗CD2增殖缺陷，SLE患者CD8+T细胞表达CD28的细胞明显减少，而CD4+细胞表达CD28的缺陷也较少。本研究提供的证据表明，SLE的某些功能性T细胞缺陷可能至少部分是由于T细胞与常规辅助细胞相互作用后CD28介导的共刺激活性降低所致。
Objective. To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect.Methods. Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb.Results. The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients, This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing, Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect, Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells.Conclusion. This study provides evidence that some functional T cell defects in SLE mag be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.