AUTOANTIBODY RESPONSES ASSOCIATED W/ SIV INFECTION

HIV感染与B功能异常有关 淋巴细胞，包括高丙种球蛋白血症，存在高 自发激活的免疫球蛋白分泌细胞的数量 循环和血清中自身抗体的存在。 的 稳定、长期激活B淋巴细胞，似乎具有特异性 对于HIV决定簇或其他抗原， 在免疫系统损伤的发病机制中的作用， 艾滋病病毒引起的疾病的过程。 本研究的目的是 艾滋病相关自身免疫现象的定义 SIV感染恒河猴模型。 我们测试了几个未感染的 和受感染动物的抗单链（ss）DNA的存在 和抗双链（ds）DNA抗体。 一般来说，抗ssDNA 抗体存在于多种自身免疫性疾病中， 少数正常个体，而抗dsDNA抗体存在于 50%至70%的系统性红斑狼疮（SLE）患者。 首先，我们检测了33只正常猕猴和21只SIV感染猕猴的血清， 通过ELISA检测抗ssDNA和抗dsDNA抗体的存在。 二是 测试了从三只SIV感染的恒河猴中收集的血清， 在感染后的两个不同时间点。 抗ssDNA和 抗dsDNA抗体由SIV感染的恒河猴产生。 样本的平均值（正常猕猴与SIV感染猕猴）为 在0.05的水平上不同。 在三只感染SIV的猕猴中， 抗DNA抗体在感染前以非常低的水平存在。 感染后滴度逐渐增加。 这些数据 证明SIV感染会引发 抗DNA抗体，因此，验证使用SIV感染 恒河猴用于研究艾滋病相关的自身免疫现象。 为了确定导致这些生产的机制， 自身抗体和测试的假设，B细胞超抗原 参与了这些机制，我们正在执行一系列 实验，其中包括分析的影响， 重组SIV抗原对B细胞活化和表达的影响 细胞表面抗原

HIV infection is associated with functional abnormalities of B lymphocytes, including hypergammaglobulinemia, presence of high numbers of spontaneously activated immunoglobulin-secreting cells in the circulation, and the presence of autoantibodies in serum. The steady, long term activation of B lymphocytes, which seems specific for either HIV determinants or other antigens, might play a crucial role in the pathogenesis of the immune system damage observed during the course of the HIV-induced disease. The objective of this study is the definition of AIDS-associated autoimmune phenomena in the SIV-infected rhesus macaque model. We have tested several uninfected and infected animals for the presence of anti-single stranded (ss) DNA and anti-double stranded (ds) DNA antibodies. In general, anti-ssDNA antibodies are present in a variety of autoimmune diseases and in a few normal individuals, whereas anti-dsDNA antibodies are present in 50% to 70% of patients with systemic lu pus erythematosus (SLE). First, we tested sera from 33 normal and 21 SIV-infected macaques for presence of anti-ssDNA and anti-dsDNA antibodies by ELISA. Second, we tested sera collected from three SIV-infected rhesus macaques prior and at two different time-points after infection. Both anti-ssDNA and anti-dsDNA antibodies are produced by SIV-infected rhesus macaques. The means of the samples (normal versus SIV-infected macaques) are different at the 0.05 level. In the three SIV-infected macaques, anti-DNA antibodies were present at very low level prior to infection. The titers progressively increased following infection. These data demonstrate that infection with SIV triggers the production of anti-DNA antibodies and, therefore, validate the use of SIV-infected rhesus macaques for the study of AIDS-related autoimmune phenomena. To define the mechanisms that lead to the production of these autoantibodies and to test the hypothesis that B cell superantigens are involved in these mechan isms, we are performing a series of experiments, which include the analysis of the effects that recombinant SIV antigens have on B cell activation and expression of cell-surface antigens.