Howell D M, Feldman M, Siegal F P, Pettera L, Fitzgerald-Bocarsly P
University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Department of Laboratory Medicine and Pathology, Newark 07103.
J Acquir Immune Defic Syndr (1988). 1993 Jan;6(1):15-23.
We have previously demonstrated that in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) by peripheral blood mononuclear cells PBMCs from patients infected with the human immunodeficiency virus (HIV-1) decreases dramatically with disease progression, with extremely low levels of IFN-alpha preceding and predictive of opportunistic infections. Natural killer (NK) lysis, however, was found to decay later in disease and often was within normal limits even when IFN-alpha production was severely compromised. The NK lysis of HSV-infected fibroblasts (HSV-FS) is dependent on an HLA-DR+ accessory cell (AC) population that shares the phenotype of the predominant IFN-alpha-producing cell (IPC) population. To determine whether there is a correlation between AC activity and IFN-alpha production in these patients, we tested the ability of PBMCs from AIDS patients to provide AC help to NK cells from heterologous donors. While NK cells were highly sensitive to gamma irradiation, AC activity was relatively radioresistant. Therefore, NK cells from healthy donors were depleted of HLA-DR+ ACs and added to irradiated PBMCs from either healthy or AIDS donors to test for the function of ACs in the irradiated populations. Irradiated cells from AIDS patients were found to provide normal AC activity despite decreased IFN-alpha production in the majority of the patients. We failed to observe NK augmenting activity in supernatants of irradiated PBMCs from IFN-deficient patients that had been stimulated with HSV-FS.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前已经证明,感染人类免疫缺陷病毒(HIV-1)患者的外周血单个核细胞(PBMC)对单纯疱疹病毒(HSV)产生的α干扰素(IFN-α)的体外产量会随着疾病进展而显著下降,在机会性感染之前和预测机会性感染时,IFN-α水平极低。然而,自然杀伤(NK)细胞的杀伤作用在疾病后期才下降,即使IFN-α产生严重受损时,其通常仍在正常范围内。HSV感染的成纤维细胞(HSV-FS)的NK细胞杀伤作用依赖于一种HLA-DR +辅助细胞(AC)群体,该群体与主要产生IFN-α的细胞(IPC)群体具有相同的表型。为了确定这些患者中AC活性与IFN-α产生之间是否存在相关性,我们测试了艾滋病患者PBMC为来自异源供体的NK细胞提供AC辅助的能力。虽然NK细胞对γ射线高度敏感,但AC活性相对抗辐射。因此,将健康供体的NK细胞去除HLA-DR + AC后,添加到来自健康或艾滋病供体的经照射的PBMC中,以测试照射群体中AC的功能。尽管大多数患者的IFN-α产生减少,但发现艾滋病患者的经照射细胞能提供正常的AC活性。我们在经HSV-FS刺激的IFN缺陷患者的经照射PBMC上清液中未观察到NK增强活性。(摘要截于250字)