猪自然杀伤T细胞研究进展
Porcine natural killer T cells
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Related Research Unit(s)
Detail(s)
Original language | Chinese (Simplified) |
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Pages (from-to) | 47-53 |
Journal / Publication | 科学通报 |
Volume | 67 |
Issue number | 1 |
Online published | 9 Oct 2021 |
Publication status | Published - Jan 2022 |
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Abstract
限制性自然杀伤T(invariant natural killer T, iNKT)细胞是一类同时表达NK与T细胞受体且具有NK细胞和T细胞两方面性质的独特淋巴细胞. 与传统T细胞不同, iNKT细胞表达高度保守的T细胞受体(小鼠: TRAV11-TRAJ18、TRBV13、TRBV29或TRBV1; 人: TRAV10-TRAJ18、TRBV25-1), 这种限制性的受体表达决定了这类细胞的抗原特异性. iNKT细胞识别由CD1d分子提呈的糖脂类抗原, 迅速分泌大量细胞因子参与机体的先天性免疫和获得性免疫反应, 因此在免疫系统中具有不可忽视的作用. 近年来研究发现, 与人和小鼠相似, 猪同样具有iNKT细胞. 然而受限于多种因素, 对于猪iNKT细胞的研究进展相对缓慢, 对其表征与功能了解也十分有限. 我们对猪iNKT细胞以及其在猪流感免疫中的作用开展了部分基础工作. 本文对有关猪iNKT细胞特征和功能的研究现状, 以及存在的问题进行综述.
Invariant natural killer T (iNKT) cells are a subset of so-called innate-like T cells that share phenotypic characteristics of both NK and conventional T cells. Unlike conventional T cells, iNKT cells express a semi-invariant T cell receptor (TCR) (TRAV10-TRAJ18/TRBV25-1 in humans and TRAV11-TRAJ18/TRBV13, TRBV29, or TRBV1 in mice) that dictates their antigen specificity. iNKT cells recognize glycolipid antigens such as α-galctosylceramide (α-GalCer) presented by the non-polymorphic major histocompatibility complex (MHC) class I-like molecule, CD1d. Once activated, they interact with and influence multiple cell types in both innate and adaptive immune systems. Immune responses induced by activated iNKT cells resemble conventional CD4+ T helper cells in many aspects. Therefore, these cells have been studied extensively particularly for their therapeutic potential to treat various infectious and inflammatory diseases, autoimmune diseases, and cancer. However, the majority of this research has employed mouse studies that have been difficult to translate into humans due in part to differences in iNKT cells between mice and humans.
Although iNKT cells have been well characterized in mice and humans, very little is known about these cells in pigs. Like human and mouse iNKT cells, porcine iNKT cells possess a memory/activation phenotype, indicated by high MHC II-SLA-DR and CD5, and low CD45RA expression. Our previous studies have characterized the phenotype, function, and TCR repertoire diversity of iNKT cells in healthy pigs. Our results show that pig and human iNKT cells are fundamentally similar for their frequency, distribution, and TCR repertoire diversity, which suggests that iNKT cells between these species play a similar role in immunity and disease. We further evaluated the adjuvant effects of iNKT cells on swine influenza vaccines and showed that α-GalCer-elicited immune responses improved influenza vaccine efficacy. Our findings also indicate that pigs offer a valuable preclinical model for understanding how iNKT cells contribute to influenza infections in humans.
Swine hold several advantages over mice as a preclinical model for iNKT cell therapy because of the many similarities between human and pig iNKT cells. In this review, we first briefly summarize the activation modes and immunoregulatory functions of iNKT cells. Then we compare the phenotype and tissue distribution of porcine iNKT cells, focusing on their similarities and differences to their counterparts in mice and humans. Lastly, we review the adjuvant effects of iNKT cell agonists and discuss some challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.
Although iNKT cells have been well characterized in mice and humans, very little is known about these cells in pigs. Like human and mouse iNKT cells, porcine iNKT cells possess a memory/activation phenotype, indicated by high MHC II-SLA-DR and CD5, and low CD45RA expression. Our previous studies have characterized the phenotype, function, and TCR repertoire diversity of iNKT cells in healthy pigs. Our results show that pig and human iNKT cells are fundamentally similar for their frequency, distribution, and TCR repertoire diversity, which suggests that iNKT cells between these species play a similar role in immunity and disease. We further evaluated the adjuvant effects of iNKT cells on swine influenza vaccines and showed that α-GalCer-elicited immune responses improved influenza vaccine efficacy. Our findings also indicate that pigs offer a valuable preclinical model for understanding how iNKT cells contribute to influenza infections in humans.
Swine hold several advantages over mice as a preclinical model for iNKT cell therapy because of the many similarities between human and pig iNKT cells. In this review, we first briefly summarize the activation modes and immunoregulatory functions of iNKT cells. Then we compare the phenotype and tissue distribution of porcine iNKT cells, focusing on their similarities and differences to their counterparts in mice and humans. Lastly, we review the adjuvant effects of iNKT cell agonists and discuss some challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.
Research Area(s)
- 猪, iNKT细胞, 流感, 免疫, Pig, INKT cells, Influenza, Immunity