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感染1型猿猴嗜T淋巴细胞病毒的恒河猴(猕猴)外周血单个核细胞中IFNγ和IL2的组成性释放

Constitutive release of IFNγ and IL2 from peripheral blood mononuclear cells of rhesus macaques (Macaca mulatta) infected with simian T-lymphotropic virus type 1.

作者信息

Yee JoAnn L, Montiel Nestor A, Ardeshir Amir, Lerche Nicholas W

机构信息

Pathogen Detection Laboratory, California National Primate Research Center, University of California, Davis, California, USA.

出版信息

Comp Med. 2013;63(6):508-14.

Abstract

Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of human T-cell lymphotropic viruses (HTLV), are endemic in many populations of African and Asian monkeys and apes. Although an etiologic link between STLV1 infection and lymphoproliferative disorders such as malignant lymphomas has been suggested in some nonhuman primate species, most STLV infections are inapparent, and infected animals remain clinically healthy. The retroviral transactivator, tax, is well known to increase transcription of viral and cellular genes, resulting in altered cytokine profiles. This study compared the cytokine profiles of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative controls. IFNγ, TNFα, IL10, and IL2 levels in unstimulated PBMC culture supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays. IFNγ concentrations were found significantly higher in the supernatants of PBMC cultures of seropositive monkeys as compared with seronegative controls. In addition, although IL2 concentrations were not significantly elevated in the supernatants of PBMC cultures of all seropositive monkeys as compared with all seronegative controls, IL2 levels were increased in a subset of 5 pairs. Increased constitutive cytokine release occurred in the absence of spontaneous proliferation. The increased constitutive release of IFNγ and IL2 suggests that STLV1 alters immune functions in infected but clinically healthy rhesus macaques and further characterizes STLV1 infection of rhesus macaques as a potential model for human HTLV1 infection.

摘要

猴T细胞嗜淋巴细胞病毒(STLV)是人类T细胞嗜淋巴细胞病毒(HTLV)的非人灵长类对应物,在非洲和亚洲许多猴子及猿类种群中呈地方性流行。尽管在一些非人灵长类物种中已表明STLV1感染与恶性淋巴瘤等淋巴增生性疾病之间存在病因学联系,但大多数STLV感染并不明显,受感染动物在临床上仍保持健康。逆转录病毒反式激活因子tax众所周知可增加病毒和细胞基因的转录,从而导致细胞因子谱改变。本研究比较了25只STLV1血清阳性恒河猴(猕猴)外周血单个核细胞(PBMC)培养物与年龄和性别匹配的血清阴性对照的细胞因子谱。在24、48和72小时时,通过酶免疫测定法测量未刺激的PBMC培养上清液中的IFNγ、TNFα、IL10和IL2水平。发现血清阳性猴子的PBMC培养上清液中的IFNγ浓度明显高于血清阴性对照。此外,尽管与所有血清阴性对照相比,所有血清阳性猴子的PBMC培养上清液中的IL2浓度没有显著升高,但在5对猴子的亚组中IL2水平有所增加。在无自发增殖的情况下发生了组成性细胞因子释放增加。IFNγ和IL2组成性释放的增加表明STLV1改变了受感染但临床上健康的恒河猴的免疫功能,并进一步将恒河猴的STLV1感染表征为人类HTLV1感染的潜在模型。

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