Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.
Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.
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DOI：
10.1084/jem.182.4.1067
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发表时间：
1995-10-01
影响因子：
15.3
通讯作者：
McDyer, John F.
中科院分区：
文献类型：
--
作者：
Seder, Robert A.;Grabstein, Kenneth H.;Berzofsky, Jay A.;McDyer, John F.
细胞因子已被证明是免疫反应的强大调节剂。在这项研究中，我们分析了新发现的细胞因子白细胞介素(IL)-15对处于不同疾病阶段的人类免疫缺陷病毒（HIV）感染者外周血单个核细胞（PBMCs）和纯化的CD4+ T细胞的增殖和细胞因子诱导的影响。我们观察到，当受到多克隆有丝分裂原、破伤风类毒素或hiv特异性抗原的刺激时，IL-15以剂量依赖的方式增强了hiv感染个体的pbmc的增殖反应。通过在IL-2受体的β链上添加中和抗体，外源性IL-15的作用大大减弱。此外，IL-15促进增殖的能力通过培养中产生的内源性IL-2的存在而增强。我们还研究了外源性IL-15对PBMC或CD4+ T细胞对有丝分裂原或破伤风类毒素的诱导IL-2、IL-4和干扰素(IFN)- γ的影响。这与外源IL-2和IL-12在相同条件下的作用进行了比较。将IL-2或IL-15添加到PBMCs或CD4+ T细胞的短期体外培养中，对IL-2、IL-4或ifn - γ的产生几乎没有影响。相比之下，IL-12在这些培养物中显著增强了IL-2和IFN- γ的产生。内源性细胞因子对ifn - γ诱导的作用也进行了研究。在抗原刺激培养中加入IL-2受体α链或IL-12的中和抗体可显著降低ifn - γ的产生。内源性IL-15的中和也导致有丝分裂原刺激培养的ifn - γ产生减少。我们评估了受丝裂原刺激的PBMCs和CD4+ T细胞产生的IL-4和ifn - γ蛋白，看看我们是否能检测到细胞因子产生的特定偏差。在CD4+ T细胞中检测到少量的IL-4，但在大多数个体的pbmc中检测不到。然而，ifn - γ和IL-2也从这些相同的培养中产生。这些结果进一步阐明了细胞因子在hiv感染个体中的调节机制，并为IL-15可能是一种有用的免疫调节剂提供了证据。
Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL- 2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN- gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator.
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DOI：
10.1084/jem.179.4.1273
发表时间：
1994-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manetti R;Gerosa F;Giudizi MG;Biagiotti R;Parronchi P;Piccinni MP;Sampognaro S;Maggi E;Romagnani S;Trinchieri G
通讯作者：
Trinchieri G
影响因子：
56.9
作者：
GRABSTEIN, KH;EISENMAN, J;GIRI, JG
通讯作者：
GIRI, JG
影响因子：
56.9
作者：
MORGAN, DA;RUSCETTI, FW;GALLO, R
通讯作者：
GALLO, R
影响因子：
15.3
作者：
Chehimi, J;Starr, S E;Frank, I;D'Andrea, A;Ma, X;MacGregor, R R;Sennelier, J;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
158.5
作者：
KOVACS, JA;BASELER, M;LANE, HC
通讯作者：
LANE, HC