Gurley R J, Ikeuchi K, Byrn R A, Anderson K, Groopman J E
New England Deaconess Hospital, Division of Hematology/Oncology, Harvard Medical School, Boston, MA.
Proc Natl Acad Sci U S A. 1989 Mar;86(6):1993-7. doi: 10.1073/pnas.86.6.1993.
The pathogenesis of cellular immune deficiency following human immunodeficiency virus (HIV) infection could result from quantitative and/or qualitative dysfunction of the CD4+ lymphocyte population. To better characterize the T-cell response to soluble antigen with HIV infection, we have isolated peripheral blood lymphocytes and purified populations of CD4+ lymphocytes from healthy HIV antibody-positive subjects, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and healthy HIV antibody-negative controls. T-lymphocyte function was determined by proliferative response to lectin (phytohemagglutinin), phorbol 12-myristate 13-acetate (PMA), calcium ionophore, purified recombinant HIV envelope gp120, tetanus toxoid antigen, and tetanus toxoid antigen in the presence of recombinant gp120 or purified recombinant soluble CD4. PBLs and CD4+ lymphocytes from asymptomatic HIV-infected subjects responded equally well to lectin, PMA, and/or calcium ionophore and to tetanus toxoid as cells from uninfected control subjects. The cells that proliferated in response to a soluble antigenic stimulus did not respond to gp120. Cells from subjects with ARC had a selective antigen recognition defect independent of the number of CD4+ lymphocytes. Recombinant gp120 inhibited CD4+ lymphocyte proliferation to antigenic stimulus by 30-40%. Recombinant soluble CD4, a proposed therapeutic for HIV, had no effect on T-cell response to antigen. A selective antigen recognition response was not compromised early in HIV infection but was compromised in subjects with ARC. Inhibition of proliferation to tetanus toxoid by gp120 suggests that HIV may affect major histocompatibility complex II restricted antigen recognition independent of CD4+ cell loss.
人类免疫缺陷病毒（HIV）感染后细胞免疫缺陷的发病机制可能源于CD4 +淋巴细胞群体的数量和/或质量功能障碍。为了更好地表征HIV感染时T细胞对可溶性抗原的反应，我们从健康的HIV抗体阳性受试者、获得性免疫缺陷综合征（AIDS）相关综合征（ARC）患者以及健康的HIV抗体阴性对照中分离出外周血淋巴细胞并纯化CD4 +淋巴细胞群体。通过对凝集素（植物血凝素）、佛波醇12 -肉豆蔻酸酯13 -乙酸酯（PMA）、钙离子载体、纯化的重组HIV包膜糖蛋白120（gp120）、破伤风类毒素抗原以及存在重组gp120或纯化的重组可溶性CD4时的破伤风类毒素抗原的增殖反应来确定T淋巴细胞功能。无症状HIV感染受试者的外周血淋巴细胞（PBL）和CD4 +淋巴细胞对凝集素、PMA和/或钙离子载体以及破伤风类毒素的反应与未感染对照受试者的细胞一样良好。对可溶性抗原刺激产生增殖反应的细胞对gp120无反应。ARC患者的细胞存在独立于CD4 +淋巴细胞数量的选择性抗原识别缺陷。重组gp120可使CD4 +淋巴细胞对抗原刺激的增殖反应抑制30 - 40%。重组可溶性CD4作为一种提议的HIV治疗药物，对T细胞对抗原的反应没有影响。HIV感染早期选择性抗原识别反应未受损，但ARC患者受损。gp120对破伤风类毒素增殖的抑制表明HIV可能影响主要组织相容性复合体II类限制的抗原识别，而与CD4 +细胞丢失无关。
