Alvarado C, Alcocer-Varela J, Llorente L, Richaud-Patin Y, Cerbon M, Alarcon-Segovia D
Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, México D.F., México City.
J Autoimmun. 1994 Dec;7(6):763-73. doi: 10.1006/jaut.1994.1060.
CD28 is a 44-kDa glycoprotein that contributes to T cell activation and proliferation. To elucidate the functional role of CD28 in T cell proliferation and IL-2 production in SLE, we studied its effects in cells from untreated patients with active (n = 10) or inactive disease (n = 10) as compared with normal subjects. Mean percentages of CD4+ CD28+ and CD8+ CD28+ T cells were decreased in SLE patients (P < 0.01). SLE patients had significantly decreased absolute CD8+ CD28+ T cells. To investigate whether CD28 antibody affects T cell proliferation, we stimulated peripheral blood T cells from SLE patients and normal controls with anti-CD28, anti-CD3 and/or Interleukin-2 (IL-2) during 3 days of culture. We found that T cells from SLE patients had significantly higher responses to CD28 than did cells from normal controls. This effect was higher in cells from patients with active disease than in those with inactive disease. Conversely, IL-2 had no significant effect on the proliferative response of SLE T cells. However, when it was used for co-stimulating with anti-CD28, there was an increase in the secretion of IL-2 which was greater in the cells of patients with active disease. Thus, on average, there was an 81% increase in the production of IL-2 in T cells from patients with active SLE, 48% in those from patients with inactive disease and 40% in T cells from healthy controls, as compared with the production in response to stimulus by anti-CD3 or with anti-CD3 and anti-CD28. Lymphocytes from patients with active disease showed increased gene expression of CD28 when compared with normal subjects. These data suggest that CD28 might play a central role in the defective immune response observed in SLE patients.
CD28是一种44千道尔顿的糖蛋白，有助于T细胞的激活和增殖。为了阐明CD28在系统性红斑狼疮（SLE）患者T细胞增殖和白细胞介素-2（IL-2）产生中的功能作用，我们研究了其在未治疗的活动性疾病患者（n = 10）或非活动性疾病患者（n = 10）的细胞中的作用，并与正常受试者进行比较。SLE患者中CD4+ CD28+和CD8+ CD28+ T细胞的平均百分比降低（P < 0.01）。SLE患者的绝对CD8+ CD28+ T细胞显著减少。为了研究CD28抗体是否影响T细胞增殖，我们在3天的培养过程中用抗CD28、抗CD3和/或白细胞介素-2（IL-2）刺激SLE患者和正常对照的外周血T细胞。我们发现，SLE患者的T细胞对CD28的反应显著高于正常对照的细胞。这种效应在活动性疾病患者的细胞中比在非活动性疾病患者的细胞中更高。相反，IL-2对SLE T细胞的增殖反应没有显著影响。然而，当它与抗CD28共同刺激时，IL-2的分泌增加，在活动性疾病患者的细胞中增加更为明显。因此，与抗CD3或抗CD3和抗CD28刺激后的产生相比，活动性SLE患者T细胞中IL-2的产生平均增加81%，非活动性疾病患者的T细胞中增加48%，健康对照的T细胞中增加40%。与正常受试者相比，活动性疾病患者的淋巴细胞显示出CD28基因表达增加。这些数据表明，CD28可能在SLE患者中观察到的免疫反应缺陷中起核心作用。
