在对草花粉过敏原过敏的小鼠中开展适应性细胞疗法

IF 3 Q3 IMMUNOLOGY
Antibodies Pub Date : 2024-06-18 DOI:10.3390/antib13020048
Anna Marianne Weijler, Lisa Prickler, Verena Kainz, Eva Bergmann, Barbara Bohle, Heinz Regele, Rudolf Valenta, Birgit Linhart, Thomas Wekerle
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引用次数: 0

摘要

I 型过敏症患者在全球人口中所占的比例不断增加,随之而来的是过敏症状患者人数的增加。最近,我们研究发现,使用表达过敏原的骨髓(BM)细胞或脾脏 B 细胞进行预防性细胞疗法,可诱导天真小鼠产生过敏原特异性耐受。在此,我们研究了细胞疗法能否调节免疫前小鼠已建立的继发性过敏原特异性免疫反应。在转移表达 Phl p 5 的 BM 细胞之前,我们先让小鼠对草花粉过敏原 Phl p 5 和来自桦树花粉的无关对照过敏原 Bet v 1 过敏。用低剂量辐照、成本刺激阻断、雷帕霉素和T细胞耗竭抗胸腺细胞球蛋白(ATG)的几种组合对小鼠进行调节。细胞转移后血清中过敏原特异性 IgE 和 IgG1 的水平通过酶联免疫吸附试验测定,细胞反应的改变通过体外增殖试验和 Phl p 5+ 皮肤移植物移植测定。测试的治疗方案均未影响 Phl p 5 特异性抗体水平。在使用大量 Phl p 5+ BMC 或在细胞治疗和皮肤移植之间没有发生致敏事件的小鼠中,观察到 Phl p 5+ 白细胞的短暂低水平嵌合以及皮肤移植存活时间明显延长。本文提供的数据表明,预先存在的继发性过敏原特异性免疫反应对细胞疗法的耐受性构成了巨大障碍,并强调了预防性方法对预防 IgE 介导的过敏症的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen.

The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5+ skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5+ leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5+ BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy.

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来源期刊
Antibodies
Antibodies IMMUNOLOGY-
CiteScore
7.10
自引率
6.40%
发文量
68
审稿时长
11 weeks
期刊介绍: Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.
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