Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors.
Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors.
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DOI：
10.1016/j.crmeth.2022.100350
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发表时间：
2022-12-19
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γ-δ（γδ）T细胞有助于许多免疫相关疾病的病理学;然而，目前还没有研究其活性的离体测定。在这里，我们建立了一种方法来表征人过敏原反应性γδ T细胞在外周血中使用激活诱导的标志物测定靶向上调4-1BB和CD 69表达。在对小鼠、蟑螂、屋尘螨和梯牧草致敏的供体中检测到广泛且可重复的离体过敏原反应性γδ T细胞应答，但该应答与非过敏参与者的应答没有差异。在54.2%-100%的过敏受试者中，以供体和过敏原特异性模式容易地检测到对4种不同过敏原提取物的反应性，并通过T细胞受体（TCR）阻断而消除。CD 40 L上调和细胞内细胞因子染色的分析揭示了对小鼠和蟑螂提取物刺激的辅助性T细胞1型（Th 1）极化反应。这些结果支持过敏原反应性γδ T细胞的存在及其在过敏性疾病中重新平衡失调的Th 2应答的潜在用途。使用外周血的离体测定可以检测人γδ T细胞应答上调的4-1BB和CD 69表达标签过敏原反应性人γδ T细胞γδ T细胞应答是供体和过敏原特异性的，并且被TCR阻断消除小鼠和蟑螂过敏原特异性γδ T细胞应答是Th 1极化的。因此，对于γδ T细胞在人类疾病中的作用，目前还没有足够的认识。在这里，我们报告了一种方法的发展，可靠地识别抗原反应性γδ T细胞在人外周血单核细胞（PBMC）的定量和定性。对过敏性和非过敏性个体中的几种过敏原提取物进行抗原反应性γδ T细胞的表征。然而，没有观察到重大差异，可能是由于过敏原提取物的复杂组成，这需要对单个抗原组分进行进一步研究。Yu等人使用离体测定表征外周血中的人γ-δ（γδ）T细胞。他们发现，对常见环境过敏原特异性的人类γδ T细胞在过敏供体中是Th 1极化的。γδ T细胞可能具有免疫调节作用，可用于调节过敏性疾病中失调的Th 2应答。
Gamma-delta (γδ) T cells contribute to the pathology of many immune-related diseases; however, no ex vivo assays to study their activities are currently available. Here, we established a methodology to characterize human allergen-reactive γδ T cells in peripheral blood using an activation-induced marker assay targeting upregulated 4-1BB and CD69 expression. Broad and reproducible ex vivo allergen-reactive γδ T cell responses were detected in donors sensitized to mouse, cockroach, house dust mite, and timothy grass, but the response did not differ from that in non-allergic participants. The reactivity to 4 different allergen extracts was readily detected in 54.2%–100% of allergic subjects in a donor- and allergen-specific pattern and was abrogated by T cell receptor (TCR) blocking. Analysis of CD40L upregulation and intracellular cytokine staining revealed a T helper type 1 (Th1)-polarized response against mouse and cockroach extract stimulation. These results support the existence of allergen-reactive γδ T cells and their potential use in rebalancing dysregulated Th2 responses in allergic diseases. Ex vivo assays using peripheral blood can detect human γδ T cell responses Upregulated 4-1BB and CD69 expression tag allergen-reactive human γδ T cells γδ T cell responses are donor and allergen specific and abrogated by TCR blocking Mouse and cockroach allergen-specific γδ T cell responses are Th1-polarized Current methodologies for studying gamma-delta (γδ) T cells are limited to clonal expansion and long-term in vitro cultures. As a result, insufficient insights are offered to fully understand the role of γδ T cells in human diseases. Here, we report the development of a methodology that reliably identifies antigen-reactive γδ T cells in human peripheral blood mononuclear cells (PBMCs) both quantitatively and qualitatively. A characterization of antigen-reactive γδ T cells was performed for several allergen extracts in allergic and non-allergic individuals. However, no major differences were observed, likely due to the complex composition of allergen extracts, which requires further studies on individual antigen components. Yu et al. characterize human gamma-delta (γδ) T cells in peripheral blood using ex vivo assays. They find that human γδ T cells specific for common environmental allergens are Th1-polarized in allergic donors. γδ T cells could be of immunotherapeutic use to rebalance dysregulated Th2 responses in allergic diseases.
DOI：
10.4049/jimmunol.1202230
发表时间：
2013-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Huang Y;Aydintug MK;Loomis J;Macleod MK;McKee AS;Kirchenbaum G;Jakubzick CV;Kedl RM;Sun D;Jacobelli J;O'Brien RL;Born WK
通讯作者：
Born WK