Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients.
Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients.
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DOI：
10.1371/journal.pone.0074326
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Luppi M
中科院分区：
文献类型：
--
作者：
Potenza L;Vallerini D;Barozzi P;Riva G;Forghieri F;Beauvais A;Beau R;Candoni A;Maertens J;Rossi G;Morselli M;Zanetti E;Quadrelli C;Codeluppi M;Guaraldi G;Pagano L;Caira M;Del Giovane C;Maccaferri M;Stefani A;Morandi U;Tazzioli G;Girardis M;Delia M;Specchia G;Longo G;Marasca R;Narni F;Merli F;Imovilli A;Apolone G;Carvalho A;Comoli P;Romani L;Latgè JP;Luppi M
在侵袭性曲霉病（IA）小鼠模型和健康供体中的几项研究表明，不同的曲霉抗原可能刺激不同的适应性免疫应答。然而，在患有该疾病的患者中尚未报道曲霉特异性T细胞的发生。在IA患者中，我们研究了感染期间：a）是否以及如何发生和发展针对不同曲霉属抗原的特异性T细胞应答; B）哪些抗原引发最高频率的保护性免疫应答，以及c）这种保护性T细胞是否可以离体扩增。研究了40例血液病患者，包括22例IA患者和18例对照。用GEL 1 p、CRF 1 p、PEP 1 p、SOD 1 p、α1- 3葡聚糖、β1- 3葡聚糖、半乳甘露聚糖等重组抗原，通过酶联免疫斑点和细胞因子分泌试验，对88例外周血（PB）标本中产生IL-10、IFN-γ、IL-4和IL-17 A的特异性T细胞进行了鉴定。通过短期培养扩增特异性T细胞。仅在IA患者中检测到针对所有抗原产生非保护性白细胞介素-10（IL-10）和保护性干扰素-γ（IFN-γ）的曲霉特异性T细胞。还显示了产生IL-4和IL-17 A的特异性T细胞的数量较低。主要针对曲霉细胞壁抗原的保护性T细胞在IA过程中倾向于增加，并与更好的临床结果相关。曲霉菌特异性T细胞可以成功地从8例IA患者的PB中产生，并且包括能够裂解曲霉菌菌丝的细胞毒性亚群。曲霉属特异性T细胞应答有助于IA免疫抑制患者中病原体的清除，曲霉属细胞壁抗原是保护性免疫应答主要靶向的抗原。通过使用上述抗原，甚至在感染期间也可以从免疫抑制患者扩增细胞毒性特异性T细胞。这些发现可用于IA患者的免疫学目的。
Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1–3glucan, β1–3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA.
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影响因子：
20.3
作者：
Perruccio, K;Tosti, A;Velardi, A
通讯作者：
Velardi, A
DOI：
10.1084/jem.20100508
发表时间：
2011-05-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ryan SO;Bonomo JA;Zhao F;Cobb BA
通讯作者：
Cobb BA
影响因子：
2.6
作者：
Arroyo, Javier;Sarfati, Jaqueline;Latge, Jean Paul
通讯作者：
Latge, Jean Paul
影响因子：
4.6
作者：
Ramadan, G;Davies, B;Keever-Taylor, CA
通讯作者：
Keever-Taylor, CA
影响因子：
20.3
作者：
Potenza, Leonardo;Vallerini, Daniela;Luppi, Mario
通讯作者：
Luppi, Mario