Hofmann B, Jakobsen K D, Odum N, Dickmeiss E, Platz P, Ryder L P, Pedersen C, Mathiesen L, Bygbjerg I B, Faber V
Department of Clinical Immunology, University Hospital, Copenhagen, Denmark.
J Immunol. 1989 Mar 15;142(6):1874-80.
We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.
我们研究了301名HIV血清阳性同性恋男性外周血淋巴细胞（PBL）对丝裂原PHA、PWM和白色念珠菌抗原的增殖反应，其中55人患有艾滋病。仅临床患病的HIV血清阳性受试者对PHA的反应降低。相比之下，大多数HIV血清阳性受试者（包括无症状组）对PWM的反应显著降低。对16名HIV血清阳性受试者的进一步分析表明，CD4和CD8 T细胞亚群的增殖反应均降低。总共选择了15名对PWM反应低的HIV血清阳性个体，其中7人患有艾滋病，8人为对照进行以下研究。研究了T3、Ti、δ受体和CD2的表达，结果显示无艾滋病的HIV血清阳性受试者中CD2受体阳性细胞的百分比增加。研究了PBL对PHA、PWM、抗CD3抗体或抗CD2抗体刺激的增殖反应，结果显示在对照组中有显著相关性，而相比之下，在艾滋病患者中只有对PHA和CD2ab的反应相关。对照组中对CD2ab和CD3ab的增殖反应大于对PHA和PWM的反应。在患者中，这些反应比PWM的反应受抑制程度小，这表明丝裂原刺激比简单刺激Ti/T3和CD2受体更复杂。对静息T细胞（即去除巨噬细胞和预激活细胞的淋巴细胞）进行了进一步研究。向这些细胞中添加PHA导致预激活并伴有IL-2R（CD25）表达，但不导致增殖。相比之下，添加与CD2受体结合的PHA加SRBC导致IL-2R表达、IL-2产生和增殖。添加PWM + SRBC未导致增殖。对26名HIV血清阳性个体（其中7人患有艾滋病，12人为血清阴性对照）的静息T细胞对PHA + SRBC的反应进行比较，结果显示在19名无艾滋病的血清阳性男性中这些反应正常或仅略有降低，而在艾滋病患者中则降低。然而，所有艾滋病患者在该检测中均显示出明确的反应。因此，对PHA和PWM反应的差异可能至少部分由PHA/CD2依赖性途径的功能至少部分保留来解释。我们认为HIV感染诱导的缺陷主要涉及T3/Ti诱导的反应。
