Marek's disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response.
Marek's disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response.
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DOI：
10.3389/fimmu.2022.973762
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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主要组织相容性复合体（MHC）单倍型是鸡对马立克氏病（MD）遗传抗性和易感性的主要决定因素之一，马立克氏病病毒（MDV）是由一种致癌性疱疹病毒引起的。为了确定与MD抗性和易感性相关的T细胞的不同功能能力，我们使用鸡IFN-γ的体外ELISPOT测定法鉴定了B19和B21 MHC单倍型鸡中MDV pp 38抗原内的免疫显性CD 4 +TCRvβ1 T细胞表位。这些新的pp 38肽用于表征与MD抗性和易感性相关的T细胞的不同功能能力。RT-PCR结果显示，细胞因子（IL-2、IL-4、IL-10）和淋巴细胞裂解相关基因（穿孔素和颗粒酶B）以抗原特异性方式上调。在MD抗性鸡（B21 MHC单倍型），抗原特异性和非特异性反应是高度偏向于Th 2反应，定义为更高水平的IL-4表达以及淋巴细胞裂解相关基因相比，在MD易感鸡系（B19 MHC单倍型）。利用CD 107 a脱颗粒试验，结果表明，MDV感染损害T细胞的细胞毒性功能，无论其遗传背景如何。综上所述，这些数据证明了对pp 38的T细胞应答类型与对疾病的抗性之间的关联，并将阐明我们对这种致癌疱疹病毒的免疫应答和诱导无菌免疫的失败的理解。
The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek’s disease (MD) which is caused by an oncogenic herpesvirus; Marek’s disease virus (MDV). To determine differential functional abilities of T cells associated with resistance and susceptibility to MD, we identified immunodominant CD4+TCRvβ1 T cell epitopes within the pp38 antigen of MDV in B19 and B21 MHC haplotype chickens using an ex vivo ELISPOT assay for chicken IFN-gamma. These novel pp38 peptides were used to characterize differential functional abilities of T cells as associated with resistance and susceptibility to MD. The results demonstrated an upregulation of cytokines (IL-2, IL-4, IL-10) and lymphocyte lysis-related genes (perforin and granzyme B) in an antigen specific manner using RT-PCR. In the MD-resistant chickens (B21 MHC haplotype), antigen-specific and non-specific response was highly skewed towards Th2 response as defined by higher levels of IL-4 expression as well as lymphocyte lysis-related genes compared to that in the MD-susceptible chicken line (B19 MHC haplotype). Using CD107a degranulation assay, the results showed that MDV infection impairs cytotoxic function of T cells regardless of their genetic background. Taken together, the data demonstrate an association between type of T cell response to pp38 and resistance to the disease and will shed light on our understanding of immune response to this oncogenic herpesvirus and failure to induce sterile immunity.