Haoting Hsu , Claudio Zanettini , Modupe Coker , Sarah Boudova , David Rach , Godfrey Mvula , Titus H. Divala , Randy G. Mungwira , Francesca Boldrin , Giulia Degiacomi , Laura Cioetto Mazzabò , Riccardo Manganelli , Miriam K. Laufer , Yuji Zhang , Luigi Marchionni , Cristiana Cairo
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引用次数: 0
摘要
Vγ9Vδ2 T 淋巴细胞具有广泛的抗微生物反应程序,甚至在出生前就能快速产生 Th1 细胞因子,因此被认为在婴儿体内对病原体起着关键作用。关于 Vδ2 细胞在出生后不久获得细胞毒性潜能的调控过程仍未得到充分研究。我们观察到,脐带血 Vδ2 细胞中穿孔素的产生与同时评估 PD-1 和 CD56 所确定的表型相关。对分选的 Vδ2 细胞碎片进行的大容量 RNA 测序表明,在穿孔素+细胞比例最高的亚群中,与细胞毒性活性和 NK 功能相关的转录本富集。在差异表达的转录本中,以前与 CD8 T 细胞效应因子分化和 NK 成熟有关的 IRF8 有可能介导 Vδ2 细胞向细胞毒性效应因子分化。我们目前和过去的研究结果都支持这样的假设,即在出生前和出生后,调节 Vδ2 细胞细胞毒性功能的机制各不相同,这可能与不同程度的微生物暴露有关。
Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential
Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56. Bulk RNA sequencing of sorted Vδ2 cell fractions indicated that transcripts related to cytotoxic activity and NK function are enriched in the subset with the highest proportion of perforin+ cells. Among differentially expressed transcripts, IRF8, previously linked to CD8 T cell effector differentiation and NK maturation, has the potential to mediate Vδ2 cell differentiation towards cytotoxic effectors. Our current and past results support the hypothesis that distinct mechanisms regulate Vδ2 cell cytotoxic function before and after birth, possibly linked to different levels of microbial exposure.
期刊介绍:
Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered.
Research Areas include:
• Antigen receptor sites
• Autoimmunity
• Delayed-type hypersensitivity or cellular immunity
• Immunologic deficiency states and their reconstitution
• Immunologic surveillance and tumor immunity
• Immunomodulation
• Immunotherapy
• Lymphokines and cytokines
• Nonantibody immunity
• Parasite immunology
• Resistance to intracellular microbial and viral infection
• Thymus and lymphocyte immunobiology
• Transplantation immunology
• Tumor immunity.