Hall R P, Leiserson W M, Chused T M, Lawley T J
J Invest Dermatol. 1984 Mar;82(3):231-4. doi: 10.1111/1523-1747.ep12260103.
Normal individuals who possess the HLA B8/DRw3 haplotype as well as patients with dermatitis herpetiformis have been found to have a number of immunologic abnormalities including decreased numbers of E rosette-positive, Fc IgG receptor-bearing lymphocytes (referred to as TG cells), and increased numbers of cells which spontaneously secrete immunoglobulin. HLA B8/DRw3-positive normal individuals also have an increased risk for the development of a number of immunologically mediated diseases. Since many of these findings are suggestive of B-cell hyperreactivity and since TG cells were initially thought to represent a portion of the T suppressor cell network, we have examined the peripheral blood mononuclear (PBM) cell populations of 14 normal HLA B8/DRw3-positive individuals, 14 patients with dermatitis herpetiformis (all of whom were HLA B8/DRw3-positive), and 9 non-HLA B8/DRw3 individuals using flow cytometry and monoclonal antibodies of the OK and Leu series directed against cell surface antigens. Normal HLA B8/DRw3 individuals were found to have a significantly lower percentage of PBM cells that expressed both OKT8 and Leu-2a when compared to normal non-HLA B8/DRw3 individuals (p less than .05 Student's t-test). When the ratio of T helper cells (OKT4 and Leu-3a) to T suppressor cells (OKT8 and Leu-2a) was calculated for each individual studied, normal HLA B8/DRw3 individuals were found to have a significantly elevated ratio (Leu-3a/Leu-2a = 2.41 +/- .16, mean +/- SEM) when compared to non-HLA selected individuals (Leu-3a/Leu-2a = 1.73 +/- .05) (p less than 0.025). In addition, normal HLA B8/DRw3 individuals had decreased numbers of TG cells when compared to normal non-HLA B8/DRw3 individuals (B8/DRw3 = 6.4 +/- .74%, non-B8/DRw3 = 13.2 +/- 1.0%, mean +/- SEM, p less than .01). In order to determine the cell surface marker characteristics of TG cells, purified TG cells from both normal HLA B8/DRw3 individuals and non-HLA B8/DRw3 individuals were studied using the Leu series monoclonal antibodies and OKM1. Good agreement was found in the percentages of cells expressing each cell surface marker between the two groups. In addition, the TG cells were found to be predominately T cells (78% Leu-1-positive), with both T helper cells (40% Leu-3a-positive) and T suppressor cells (30% Leu-2a-positive) present. These results suggest that the suppressor cell activity associated with the TG subset is not due to a depletion of the T helper cell subset, and that the decreased numbers of TG cells in HLA B8/DRw3 individuals is not due to a preferential loss of cells bearing Leu-1, Leu-2a, Leu-3a, or OKM1.(ABSTRACT TRUNCATED AT 400 WORDS)
已发现拥有HLA B8/DRw3单倍型的正常个体以及疱疹样皮炎患者存在一些免疫异常,包括E花环阳性、携带Fc IgG受体的淋巴细胞(称为TG细胞)数量减少,以及自发分泌免疫球蛋白的细胞数量增加。HLA B8/DRw3阳性的正常个体发生多种免疫介导疾病的风险也增加。由于这些发现中的许多都提示B细胞反应过度,并且由于TG细胞最初被认为代表T抑制细胞网络的一部分,我们使用针对细胞表面抗原的OK和Leu系列单克隆抗体,通过流式细胞术检测了14名HLA B8/DRw3阳性正常个体、14名疱疹样皮炎患者(均为HLA B8/DRw3阳性)和9名非HLA B8/DRw3个体的外周血单个核(PBM)细胞群体。与非HLA B8/DRw3正常个体相比,HLA B8/DRw3正常个体中同时表达OKT8和Leu-2a的PBM细胞百分比显著降低(p小于0.05,Student t检验)。在计算每个研究个体的T辅助细胞(OKT4和Leu-3a)与T抑制细胞(OKT8和Leu-2a)的比例时,发现HLA B8/DRw3正常个体的比例显著升高(Leu-3a/Leu-2a = 2.41±0.16,平均值±标准误),相比之下非HLA选择个体的比例为(Leu-3a/Leu-2a = 1.73±0.05)(p小于0.025)。此外,与非HLA B8/DRw3正常个体相比,HLA B8/DRw3正常个体的TG细胞数量减少(B8/DRw3 = 6.4±0.74%,非B8/DRw3 = 13.2±1.0%,平均值±标准误,p小于0.01)。为了确定TG细胞的细胞表面标志物特征,使用Leu系列单克隆抗体和OKM1研究了来自HLA B8/DRw3正常个体和非HLA B8/DRw3个体的纯化TG细胞。两组之间表达每种细胞表面标志物的细胞百分比具有良好的一致性。此外,发现TG细胞主要是T细胞(78% Leu-1阳性),同时存在T辅助细胞(40% Leu-3a阳性)和T抑制细胞(30% Leu-2a阳性)。这些结果表明,与TG亚群相关的抑制细胞活性不是由于T辅助细胞亚群的耗竭,并且HLA B8/DRw3个体中TG细胞数量的减少不是由于携带Leu-1、Leu-2a、Leu-3a或OKM1的细胞优先丢失。(摘要截短至400字)