Chatenoud L, Volpini W, Timsit J, Boitard C, Bach J F
Department of Immunology, INSERM U25, Hopital Necker, Paris, France.
Diabetes. 1993 Jun;42(6):869-75. doi: 10.2337/diab.42.6.869.
The monoclonal antibodies 2H4 and 4B4 are specifically directed against CD45RA and CD29 antigens, respectively, which are expressed on both CD4+ and CD8+ lymphocytes. We used them to monitor the distribution of these T-cell subsets in 19 recent-onset IDDM patients (26 +/- 7 yr of age [mean +/- SD throughout]) receiving cyclosporin, and who had been treated with insulin for < 1 mo. Blood samples were examined before starting cyclosporin and after 3 and 9-12 mo of therapy. CD45RA and CD29 are expressed on distinct subsets of CD4+ T-cells, whereas in both healthy subjects and IDDM patients, 2H4 and 4B4 labeling does not always differentiate two distinct CD8+ populations. Various proportions of double-labeled CD8+ CD45RA+ CD29+ cells were detected in 59% of IDDM patients and 70% of healthy control subjects. Before cyclosporin treatment, recent-onset IDDM patients had a significantly lower proportion of CD4+CD29+ cells than the healthy control subjects (42 +/- 11 vs. 52 +/- 9%, P < 0.004). This imbalance corresponded to a significant increase in the CD4+ CD45RA+/CD4+ CD29+ ratio in the IDDM patients (1.37 +/- 0.93 vs. 0.78 +/- 0.36, P < 0.014). Independent of the presence of double-labeled cells, the proportion of CD8+ lymphocytes expressing CD45RA was significantly higher in the patients than in control subjects (72 +/- 15 vs. 57 +/- 15%, P < 0.004). The mean density of the CD45RA antigen (but not that of CD29) on both CD4+ and CD8+ cells was significantly higher in the IDDM patients before treatment than in the healthy control subjects. Cyclosporin induced complete or partial remission of the disease in 12 of 19 patients at 4-6 mo of treatment, but did not correct the imbalance between the regulatory T-cell subsets, regardless of clinical effectiveness. Cyclosporin use was associated with a significant decrease in CD45RA antigen density on both CD4+ and CD8+ T-cells.
单克隆抗体2H4和4B4分别特异性针对CD45RA和CD29抗原，这两种抗原在CD4⁺和CD8⁺淋巴细胞上均有表达。我们用它们来监测19例近期发病的胰岛素依赖型糖尿病（IDDM）患者（年龄26±7岁[ throughout表示 throughout the study，即整个研究过程中]）在接受环孢素治疗且胰岛素治疗时间<1个月时这些T细胞亚群的分布情况。在开始使用环孢素之前以及治疗3个月和9 - 12个月后采集血样进行检测。CD45RA和CD29在不同的CD4⁺T细胞亚群上表达，而在健康受试者和IDDM患者中，2H4和4B4标记并不总能区分两个不同的CD8⁺群体。在59%的IDDM患者和70%的健康对照受试者中检测到不同比例的双标记CD8⁺CD45RA⁺CD29⁺细胞。在使用环孢素治疗前，近期发病的IDDM患者CD4⁺CD29⁺细胞的比例显著低于健康对照受试者（42±11%对52±9%，P<0.004）。这种失衡对应于IDDM患者中CD4⁺CD45RA⁺/CD4⁺CD29⁺比值的显著增加（1.37±0.93对0.78±0.36，P<0.014）。与是否存在双标记细胞无关，患者中表达CD45RA的CD8⁺淋巴细胞比例显著高于对照受试者（72±15%对57±15%，P<0.004）。治疗前，IDDM患者CD4⁺和CD8⁺细胞上CD45RA抗原的平均密度（但CD29抗原的平均密度并非如此）显著高于健康对照受试者。在治疗4 - 6个月时，环孢素使19例患者中的12例实现了疾病的完全或部分缓解，但无论临床疗效如何，均未纠正调节性T细胞亚群之间的失衡。使用环孢素与CD4⁺和CD8⁺T细胞上CD45RA抗原密度的显著降低相关。
