The Pirbright Institute, Woking, United Kingdom.
Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2023 Sep 8;14:1197746. doi: 10.3389/fimmu.2023.1197746. eCollection 2023.
Infectious Bursal Disease Virus (IBDV) causes immunosuppression in chickens. While B-cell destruction is the main cause of humoral immunosuppression, bursal T cells from IBDV-infected birds have been reported to inhibit the mitogenic response of splenocytes, indicating that some T cell subsets in the infected bursa have immunomodulatory activities. CD4CD25TGFβ cells have been recently described in chickens that have immunoregulatory properties and play a role in the pathogenesis of Marek's Disease Virus.
To evaluate if CD4CD25TGFβ cells infiltrated the bursa of Fabricius (BF) following IBDV infection, and influenced the outcome of infection, birds were inoculated at either 2 days or 2 weeks of age with vaccine strain (228E), classic field strain (F52/70), or PBS (mock), and bursal cell populations were quantified by flow cytometry.
Both 228E and F52/70 led to atrophy of the BF, a significant reduction of Bu1-B cells, and a significant increase in CD4 and CD8α T cells in the BF, but only F52/70 caused suppression of immune responses to a test antigen in younger birds, and clinical signs in older birds. Virus was cleared from the BF more rapidly in younger birds than older birds. An infiltration of CD4CD25T cells into the BF, and elevated expression of bursal TGFβ-1 mRNA was observed at all time points following infection, irrespective of the strain or age of the birds, but CD4TGFβcells and CD4CD25TGFβ cells only appeared in the BF at 28 dpi in younger birds. In older birds, CD4TGFβ cells and CD4CD25TGFβ cells were present at earlier time points, from 7dpi following 228E infection, and from 14 and 28 dpi following F52/70 infection, respectively.
Our data suggest that an earlier infiltration of CD4TGFβ cells into the BF correlated with a delayed clearance of virus. However, the influx of CD4TGFβ cells and CD4CD25TGFβ into the BF did not correlate with increased pathogenicity, or immunosuppression.
传染性法氏囊病病毒（IBDV）可导致鸡的免疫抑制。虽然 B 细胞破坏是体液免疫抑制的主要原因，但已报道来自 IBDV 感染鸟类的法氏囊 T 细胞抑制脾细胞的有丝分裂反应，表明感染法氏囊中的某些 T 细胞亚群具有免疫调节活性。最近在鸡中描述了具有免疫调节特性并在马立克氏病病毒发病机制中起作用的 CD4CD25TGFβ 细胞。
为了评估 IBDV 感染后 CD4CD25TGFβ 细胞是否浸润法氏囊（BF）并影响感染结果，将雏鸡在 2 天或 2 周龄时用疫苗株（228E）、经典野毒株（F52/70）或 PBS（模拟）接种，并通过流式细胞术定量法氏囊细胞群。
228E 和 F52/70 均导致 BF 萎缩，Bu1-B 细胞显著减少，BF 中的 CD4 和 CD8α T 细胞显著增加，但只有 F52/70 导致幼龄鸟类对测试抗原的免疫反应受到抑制，并在老龄鸟类中出现临床症状。年轻鸟类比老年鸟类更快地从 BF 中清除病毒。感染后所有时间点均观察到 CD4CD25T 细胞浸润 BF，并升高法氏囊 TGFβ-1 mRNA 的表达，无论鸟类的品系或年龄如何，但年轻鸟类仅在 28dpi 时才在 BF 中出现 CD4TGFβ 细胞和 CD4CD25TGFβ 细胞。在老年鸟类中，CD4TGFβ 细胞和 CD4CD25TGFβ 细胞分别在感染 228E 后 7dpi 和感染 F52/70 后 14 和 28dpi 更早出现。
我们的数据表明，CD4TGFβ 细胞更早浸润 BF 与病毒清除延迟相关。然而，CD4TGFβ 细胞和 CD4CD25TGFβ 细胞涌入 BF 与致病性增加或免疫抑制无关。
