AI Article Synopsis
- Congenital avian leukosis virus subgroup J (ALV-J) infection in chickens leads to persistent immunotolerance, but the mechanisms are not fully understood.
- The study establishes that ALV-J infection results in increased levels of activated CD4CD25 Tregs, which play a key role in maintaining this immunotolerance.
- Infected chicks exhibit immune system imbalances, including persistent viremia, alterations in T and B cell populations, and increased expression of inhibitory cytokines, suggesting that Tregs inhibit B cell functions, contributing to long-term immunotolerance.
Article 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 CD4CD25 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 CD4CD25 Tregs in blood and immune organs significantly increased, and the frequency of CD4CD25 Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4CD25 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 CD4CD25 Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4CD25 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442411 | PMC |
| http://dx.doi.org/10.1186/s13567-021-00989-9 | DOI Listing |
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