A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS).
A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS).
复制标题
获得性免疫缺陷综合征 (AIDS) 发展过程中主要组织相容性复合体自限制性 T 细胞免疫反应选择性丧失的模型。
作者：
G. Shearer;D. Bernstein;K. Tung;C. Via;R. Redfield;S. Salahuddin;R. Gallo
来自高危HTLV-III抗体阴性和抗体阳性供体以及来自获得性免疫缺陷综合征（AIDS）、淋巴结病综合征（LAS）、通过体外诱导细胞毒性T淋巴细胞（CTL）和对流感病毒（S + X）的HLA自限性抗原的增殖反应，进行了抗艾滋病相关复合物（ARC）的研究和非自身限制性HLA同种抗原（ALLO）。所有40个抗体阴性供者均对S + X和ALLO产生CTL应答，而14个抗体阳性供者中有6个、3个LAS中有2个、5个ARC中有4个和17个AIDS患者中有7个表现出对S + X选择性缺乏CTL，但对ALLO产生正常或升高的CTL应答。在其余10名艾滋病患者中，9名对S + X或ALLO均无反应，1名对S + X和ALLO均有反应。我们还观察到抗体阳性供体最初对S + X和ALLO产生CTL应答，但随着时间的推移，S + X应答消失。我们能够恢复选择性损失的S + X CTL活性在体外加入IL 2，并在一定程度上，通过与S + X加ALLO共刺激。从健康抗体阴性供体的PBL中去除CD 4 + T辅助细胞和自体抗原呈递细胞表明，人PBL中存在不同的T辅助细胞亚群，S + X应答必须使用CD 4 + T辅助细胞群，而ALLO应答可以利用替代的CD 4- T辅助细胞途径。提出了一个模型，表明在艾滋病的发展阶段的CD 4 + T辅助细胞功能的选择性耗竭。辅助性T细胞对自身限制性抗原活性的功能测试可能是AIDS发展中免疫功能丧失的最早指标，并且可能先于CD 4+细胞绝对数量的减少。
Functional analyses of peripheral blood leukocytes (PBL) from high risk HTLV-III antibody-negative and antibody-positive donors, as well as from patients with acquired immune deficiency syndrome (AIDS), lymphadenopathy syndrome (LAS), and AIDS-related complex (ARC) were performed by the in vitro generation of cytotoxic T lymphocyte (CTL) and proliferative responses to the HLA self-restricted antigens of influenza virus (S + X) and to nonself restricted HLA alloantigens (ALLO). All 40 antibody-negative donors tested responded to both S + X and ALLO in the CTL response, whereas six of 14 antibody-positive, two of three LAS, four of five ARC, and seven of 17 AIDS patients exhibited a selective absence of CTL to S + X, but generated normal or elevated CTL responses to ALLO. Of the remaining 10 AIDS patients, nine did not respond to either S + X or ALLO, and one responded to both S + X and ALLO. A similar selective loss of the proliferative response to S + X was found. We also observed antibody-positive donors who initially generated CTL responses to S + X and ALLO, but lost the S + X response as a function of time. We were able to restore the selective loss of S + X CTL activity in vitro by the addition of IL 2 and, to some extent, by co-stimulation with S + X plus ALLO. Depletion of CD4+ T helper cells and removal of autologous antigen-presenting cells from the PBL of healthy antibody-negative donors indicated that distinct T helper cell subsets exist in human PBL, and that S + X responses must use a CD4+ T helper population, whereas ALLO responses can utilize an alternate CD4- T helper pathway. A model is presented indicating the selective depletion of CD4+ T helper function in the developmental stages of AIDS. The functional test for T helper activity to self restricted antigens may be the earliest indicator of immune functional loss in the development of AIDS, and may precede a reduction in the absolute number of CD4+ cells.