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异体造血干细胞移植后念珠菌感染患者中作为潜在免疫疗法的抗念珠菌T细胞的产生与特性分析

Generation and characterization of anti-Candida T cells as potential immunotherapy in patients with Candida infection after allogeneic hematopoietic stem-cell transplant.

作者信息

Tramsen Lars, Beck Olaf, Schuster Friedhelm R, Hunfeld Klaus-Peter, Latgé Jean-Paul, Sarfati Jacqueline, Röger Frauke, Klingebiel Thomas, Koehl Ulrike, Lehrnbecher Thomas

机构信息

Pediatric Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, D-60590, Germany.

出版信息

J Infect Dis. 2007 Aug 1;196(3):485-92. doi: 10.1086/519389. Epub 2007 Jun 18.

DOI:10.1086/519389
PMID:17597464
Abstract

Because lymphocytes play a major role in the host response to Candida infection, adoptive transfer of anti-Candida T cells might be a therapeutic option in patients undergoing allogeneic hematopoietic stem-cell transplant (alloHSCT) who have invasive Candida infection. Using the interferon (IFN)- gamma secretion assay, we isolated human anti-Candida T cells after stimulation with a cellular extract of C. albicans. These cells were expanded within 4 weeks to an average number of 2.6x107 T helper 1 type lymphocytes and significantly lost their alloreactive potential, compared with the original cell population. The generated cells were also stimulated by antigens of C. tropicalis but not by antigens of C. glabrata or various molds. In addition, generated anti-Candida T cells were able to induce damage to C. albicans hyphae and significantly increased hyphal damage induced by human neutrophils. Our data suggest that the generation of functionally active anti-Candida T cells is feasible and may be a promising treatment option for patients undergoing alloHSCT.

摘要

由于淋巴细胞在宿主对念珠菌感染的反应中起主要作用,对于接受异基因造血干细胞移植(alloHSCT)且发生侵袭性念珠菌感染的患者,过继转移抗念珠菌T细胞可能是一种治疗选择。我们使用干扰素(IFN)-γ分泌测定法,在用白色念珠菌细胞提取物刺激后分离出人类抗念珠菌T细胞。与原始细胞群体相比,这些细胞在4周内扩增至平均2.6×107个辅助性T1型淋巴细胞,且其同种异体反应潜能显著丧失。所产生的细胞也受到热带念珠菌抗原的刺激,但不受光滑念珠菌抗原或各种霉菌抗原的刺激。此外,所产生的抗念珠菌T细胞能够诱导白色念珠菌菌丝损伤,并显著增加人类中性粒细胞诱导的菌丝损伤。我们的数据表明,产生功能活跃的抗念珠菌T细胞是可行的,对于接受alloHSCT的患者可能是一种有前景的治疗选择。

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