Regulatory T cells as adjuvant target for enhancing the viral disease vaccine efficacy.
Regulatory T cells as adjuvant target for enhancing the viral disease vaccine efficacy.
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DOI：
10.1007/s13337-013-0187-3
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Bayry, Jagadeesh
中科院分区：
文献类型：
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作者：
Bayry, Jagadeesh
CD4+CD25+FoxP3+调节性T细胞（Tregs）对免疫稳态和耐受至关重要。然而，由于其抑制抗原呈递细胞（APC）、T细胞和B细胞的能力，Tregs也可以抑制对病毒和疫苗的保护性免疫反应。一些病毒已经被证明利用treg来逃避免疫反应。通过调节APC，特别是通过削弱树突状细胞的功能，如它们分泌极化细胞因子和共刺激分子表达的能力，病毒可以支持treg的分化和扩增。值得注意的是，作为概念的证明，treg的消耗显著增强了对病毒和疫苗的保护性免疫反应，这表明treg是增强疫苗免疫原性的可行靶点。由于Treg的耗竭或其功能的抑制可能导致有害的自身免疫性疾病和炎症性疾病，任何基于Treg的疫苗接种方法都不应以Treg的耗竭为目标，对Treg功能的抑制应该是短暂的。最近的研究针对treg上表达的CCR4与其配体CCL22和CCL17之间的相互作用，暂时抑制免疫部位treg的募集。重要的是，在实验模型中使用CCR4拮抗剂作为“分子佐剂”，当与各种疫苗抗原联合注射时，可扩增细胞和体液免疫反应。在不同的模型中观察到显著的佐剂活性而没有明显的副作用，这有力地证明了CCR4是合理佐剂设计的可持续靶点。
CD4+CD25+FoxP3+ regulatory T cells (Tregs) are critical for immune homeostasis and tolerance. However, because of their capacity to suppress antigen presenting cells (APC), T and B cells, Tregs could also inhibit protective immune responses to viruses and vaccines. Several viruses have been shown to exploit Tregs to evade immune response. By modulating APC and in particular by weakening the functions of dendritic cells such as their ability to secrete polarizing cytokines and expression of co-stimulatory molecules, viruses could support differentiation and expansion of Tregs. Of note, as a proof of concept, depletion of Tregs significantly enhanced the protective immune response to viruses and vaccines suggesting that Tregs are viable targets to enhance immunogenicity of vaccines. As Treg depletion or inhibition of their functions could lead to deleterious autoimmune and inflammatory disorders, any Treg-based approach for vaccination should not aim at depletion of Tregs and inhibition of their functions should be transient. Recent studies have targeted the interaction between CCR4 expressed on Tregs and its ligands CCL22 and CCL17 to inhibit transiently the recruitment of Tregs at the site of immunization. Importantly, use of CCR4 antagonists as ‘molecular adjuvants’ in vivo in experimental models, amplified cellular and humoral immune responses when injected in combination with various vaccine antigens. The significant adjuvant activity observed in diverse models without noticeable side effects provided strong evidence that CCR4 is a sustainable target for rational adjuvant design.
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作者：
Maizels RM;Smith KA
通讯作者：
Smith KA
DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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抗原特异性记忆调节CD4+ FOXP3+ T细胞控制对流感病毒感染的记忆反应。
DOI：
10.4049/jimmunol.1203140
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Brincks EL;Roberts AD;Cookenham T;Sell S;Kohlmeier JE;Blackman MA;Woodland DL
通讯作者：
Woodland DL
DOI：
10.4049/jimmunol.1101649
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Kastenmuller W;Gasteiger G;Subramanian N;Sparwasser T;Busch DH;Belkaid Y;Drexler I;Germain RN
通讯作者：
Germain RN
DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D