Giscombe R, Nityanand S, Lewin N, Grunewald J, Lefvert A K
Immunological Research Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Clin Immunol. 1998 Nov;18(6):404-13. doi: 10.1023/a:1023230722874.
Patients with Wegener's granulomatosis have a high prevalence of expanded populations of CD4+ and CD8+ T cells bearing different alpha/beta T cell receptors. To elucidate the role of these populations, we studied the phenotypic and functional characteristics of 13 expanded T cell populations in four patients for a period of 35-51 months. The expanded populations generally showed a persistently high expression of the activation markers HLA-DR and CD25. This expression was independent of the activity of the disease. The expanded populations also expressed CD45RO and/or CD45RA and most of them expressed CD57 but not CD28. Analysis of intracellular presence and secretion of IFN-gamma, IL-2, and IL-4 showed that most of the expanded cell populations contained and/or secreted more of these cytokines than the nonexpanded populations, with an especially high expression/secretion of IFN-gamma and IL-2. The expanded populations showed little proliferative response to Con A and OKT3. The proliferative response of the cells was partly restored after preincubation in medium alone. Some of the expanded populations were associated with disease activity, thus suggesting a link between expanded T cells and the disease. The activated status of the expanded populations and the tendency for certain populations to correlate in magnitude with disease activity suggest their involvement in the disease process. The relative stability of these cell populations indicates that the stimulus driving them is persistent, in agreement with the chronicity of the disease.
韦格纳肉芽肿病患者中，携带不同α/β T细胞受体的CD4⁺和CD8⁺ T细胞群体有较高的患病率。为了阐明这些群体的作用，我们研究了4例患者中13个扩增的T细胞群体的表型和功能特征，为期35 - 51个月。扩增的群体通常显示激活标志物HLA - DR和CD25持续高表达。这种表达与疾病活动无关。扩增的群体还表达CD45RO和/或CD45RA，并且大多数表达CD57但不表达CD28。对细胞内IFN - γ、IL - 2和IL - 4的存在及分泌情况分析表明，与未扩增的群体相比，大多数扩增的细胞群体含有和/或分泌更多的这些细胞因子，尤其是IFN - γ和IL - 2有较高的表达/分泌。扩增的群体对刀豆蛋白A和OKT3的增殖反应较弱。细胞在单独的培养基中预孵育后，其增殖反应部分恢复。一些扩增的群体与疾病活动相关，因此提示扩增的T细胞与疾病之间存在联系。扩增群体的激活状态以及某些群体在数量上与疾病活动相关的趋势表明它们参与了疾病过程。这些细胞群体的相对稳定性表明驱动它们的刺激是持续存在的，这与疾病的慢性病程相符。
