High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection
Abstract Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that congenital ALV-J infection induces the production of high-frequency and activated CD4+CD25+ Tregs that...
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doaj-5df61d4658c94200a16b57efd4c014582021-09-19T11:07:27ZengBMCVeterinary Research1297-97162021-09-0152111510.1186/s13567-021-00989-9High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infectionShuhai He0Gaoying Zheng1Defang Zhou2Li Huang3Jianguo Dong4Ziqiang Cheng5College of Veterinary Medicine, Shandong Agricultural UniversityCollege of Veterinary Medicine, Shandong Agricultural UniversityCollege of Veterinary Medicine, Shandong Agricultural UniversityCollege of Husbandry and Veterinary, Xinyang Agriculture and Forestry UniversityCollege of Husbandry and Veterinary, Xinyang Agriculture and Forestry UniversityCollege of Veterinary Medicine, Shandong Agricultural UniversityAbstract Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that congenital ALV-J infection induces the production of high-frequency and activated CD4+CD25+ Tregs that maintain persistent immunotolerance. A model of congenital infection by ALV-J was established in fertilized eggs, and hatched chicks showed persistent immunotolerance characterized by persistent viremia, immune organ dysplasia, severe imbalance of the ratio of CD4+/CD8+ T cells in blood and immune organs, and significant decrease in CD3+ T cells and Bu-1+ B cells in the spleen. Concurrently, the mRNA levels of IL-2, IL-10, and IFN-γ showed significant fluctuations in immune organs. Moreover, the frequency of CD4+CD25+ Tregs in blood and immune organs significantly increased, and the frequency of CD4+CD25+ Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4+CD25+ Tregs increased in the marginal zone of splenic nodules in ALV-J-infected chickens and dispersed to the germinal center. In addition, the proliferation and activation of B cells in splenic nodules was inhibited, and the number of IgM+ and IgG+ cells in the marginal zone significantly decreased. We further found that the mRNA levels of TGF- β and CTLA-4 in CD4+CD25+ Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4+CD25+ Tregs inhibited B cells functions by expressing the inhibitory cytokine TGF-β and inhibitory surface receptor CTLA-4, thereby maintaining persistent immunotolerance in congenital ALV-J-infected chickens.https://doi.org/10.1186/s13567-021-00989-9Avian leukosis virus subgroup JCD4+CD25+ Tregsviremiaimmunotolerance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuhai He Gaoying Zheng Defang Zhou Li Huang Jianguo Dong Ziqiang Cheng |
spellingShingle |
Shuhai He Gaoying Zheng Defang Zhou Li Huang Jianguo Dong Ziqiang Cheng High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection Veterinary Research Avian leukosis virus subgroup J CD4+CD25+ Tregs viremia immunotolerance |
author_facet |
Shuhai He Gaoying Zheng Defang Zhou Li Huang Jianguo Dong Ziqiang Cheng |
author_sort |
Shuhai He |
title |
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection |
title_short |
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection |
title_full |
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection |
title_fullStr |
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection |
title_full_unstemmed |
High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection |
title_sort |
high-frequency and activation of cd4+cd25+ t cells maintain persistent immunotolerance induced by congenital alv-j infection |
publisher |
BMC |
series |
Veterinary Research |
issn |
1297-9716 |
publishDate |
2021-09-01 |
description |
Abstract Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that congenital ALV-J infection induces the production of high-frequency and activated CD4+CD25+ Tregs that maintain persistent immunotolerance. A model of congenital infection by ALV-J was established in fertilized eggs, and hatched chicks showed persistent immunotolerance characterized by persistent viremia, immune organ dysplasia, severe imbalance of the ratio of CD4+/CD8+ T cells in blood and immune organs, and significant decrease in CD3+ T cells and Bu-1+ B cells in the spleen. Concurrently, the mRNA levels of IL-2, IL-10, and IFN-γ showed significant fluctuations in immune organs. Moreover, the frequency of CD4+CD25+ Tregs in blood and immune organs significantly increased, and the frequency of CD4+CD25+ Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4+CD25+ Tregs increased in the marginal zone of splenic nodules in ALV-J-infected chickens and dispersed to the germinal center. In addition, the proliferation and activation of B cells in splenic nodules was inhibited, and the number of IgM+ and IgG+ cells in the marginal zone significantly decreased. We further found that the mRNA levels of TGF- β and CTLA-4 in CD4+CD25+ Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4+CD25+ Tregs inhibited B cells functions by expressing the inhibitory cytokine TGF-β and inhibitory surface receptor CTLA-4, thereby maintaining persistent immunotolerance in congenital ALV-J-infected chickens. |
topic |
Avian leukosis virus subgroup J CD4+CD25+ Tregs viremia immunotolerance |
url |
https://doi.org/10.1186/s13567-021-00989-9 |
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