IMMUNOREGULATORY MECHANISMS IN THE RHEUMATIC DISEASES

其目的是表征免疫调节异常， 结缔组织病患者。 我们的研究最初集中在 在具有高密度Fc受体的人血淋巴细胞亚群上， 我们称之为“L细胞。“这些淋巴细胞是 种群特征为独特的形态外观， 与识别III型补体的单克隆抗体反应 受体（CR 3）。 我们计划分离L细胞和其他CR 3+淋巴细胞 亚群，确定它们与T细胞的关系，并确定它们的 对系统性狼疮患者B细胞活性的调节作用 红斑。 我们最近观察到，来自同时具有活性和非活性的患者的淋巴细胞， 和非活动性SLE患者产生白细胞介素2的能力受损， 体外 此外，这些患者自发激活T8+ 抑制IL-2产生的淋巴细胞。 我们计划确定 这是SLE的一种遗传性原发性免疫缺陷， 疾病的第二个表现。 这将由一个 SLE双胞胎研究 我们的最后一个目标是确定IL-2缺陷与 系统性红斑狼疮患者B淋巴细胞高活性。 这将通过 确定白细胞介素2对调节淋巴细胞的作用， 产生B细胞生长因子并对B细胞有直接作用 功能协调发展的 我们将确定CR 3+淋巴细胞是否参与了 这些调节电路。 这些研究应该会带来更好的 了解结缔组织病患者的发病机制 组织疾病

The objective has been to characterized immunoregulatory abnormalities in patients with connective tissue diseases. Our studies originally focused on a subset of human blood lymphocytes with high density Fc receptors for IgG which we called "L cells." These lymphocytes are part of a larger population characterized by a unique morphological appearance and which react with monoclonal antibodies which recognize the Type III complement receptor (CR3). We plan to separate L cells and other CR3+ lymphocyte subsets, determine their relationship with T cells and determine their regulatory effects on B cell activity in patients with Systemic Lupus Erythematosus. We have recently observed that lymphocytes from patients with both active and inactive SLE have an impaired capacity to produce interleukin 2 in vitro. Moreover, these patients have spontaneously activated T8+ lymphocytes that inhibit IL-2 production. We plan to determine whether this is an inherited, primary immunologic defect in SLE or whether it is a secondary manifestation of the disease. This will be accomplished by a study of Twins with SLE. Our last objective is to determine the relationship of the IL-2 defect and B lymphocyte hyperactivity in SLE. This will be accomplished by determining the effects of interleukin 2 on lymphocytes which regulate the production of B cell growth factors and which have direct effects on B cell functions. We will determine whether CR3+ lymphocytes are involved in these regulatory circuits. These studies should lead to a better understanding of pathogenetic mechanisms in patients with the connective tissue diseases.