The Role Of CD4~+CD25~+ Regulatory T Cells In The Persistent Infection Of Porcine Circovirs Type2

Porcine circovirus type 2(PCV2)-associated diseases(PCVAD), caused by PCV2, is one of the most important infectious diseases seriously endangering the global pig production. PCV2 can lead to immunosuppression and keep persistent infection in pig. However, our understanding of the mechanism of PCV2 persistence infection is still not enough at present. CD4+CD25+ regulatory T cells(Tregs) play dual roles in pathopoiesis and persistent infection of pathogenic microorganism. The objective of this study is to to figure out the role of Tregs in PCV2 persistent infection in vivo through evaluating the effect of Tregs on host immune function and virus infection.One hundred and sixty, 6-week old femal BALB/c mice were randomly divided into four groups of 42, namly Blank control(Blank), PCV2, Foxp3-sh RNA+PCV2(sh RNA+PCV2) and Foxp3+PCV2, respectively. Except Blank group, other groups were infected with PCV2 of 1.0′105.7 TCID50 by intraperitoneal injection. Each mouse from the groups of sh RNA+PCV2 and Foxp3+PCV2 was inoculated 100 μg eukaryotic plasmids expressed Foxp3-sh RNA or Foxp3 protein, respectively. Average expression levels of Foxp3 m RNA were higher than those of sh RNA+PCV2 and Blank groups following PCV2 infection, which was accompanied by the more virual load in lungs of mice from the group of Foxp3+PCV2 than that of PCV2 and sh RNA+PCV2 groupsThe proliferation activity of CD4+and CD8+T cells decreased on day 4 post-infection(dpi). The increasing of Foxp3 expression could enhance momentarily the pecific proliferation activity of CD4+ T cells while inhibit that of CD8+ T in a long time. PCV2 did not influence the specific proliferation activity of CD4+CD25+ regulatory T cells, but this proliferation activity just was lifted briefly while expression of Foxp3 was being increased. Moreover, PCV2 resulted in the levels of IFN-γ reduced and the secretions of IL-10, TGF-β1 and IL-17 A in serum from the groups of Foxp3+PCV2 and PCV2 were significantly higher than the groups of Blank and sh RNA+PCV2 by ELISA(P<0.05). PCV2 leaded tothe percentage of CD3-CD4-CD8+,CD3-CD4-CD8+ declined at the initial stage of infection and resulted in the average levels of CD3+CD4-CD8+ and CD3+CD4+CD8+ T cell subsets droped where as that of CD4+CD25+CD127Low T cell subsets increased by Flow cytometry. And the increase of Foxp3 expression impeled CD3+CD4+CD8-T, CD3+CD4-CD8+ T cells and CD3+CD4+CD8+ T cells subsets further decreased in a short time. The content of CD3-CD4-CD8+ cells rose when expression of Foxp3 was inhibited.PCV2 could cause the magnitude of CD4+CD25+ regulatory T cells increase and promote the secretion of IL-10, TGF-β1 and IL-17 A. The PCV2 load increasedin the lung and the specific and natural cellular immunity were further inhibited when the increase of Foxp3 expression. These results indicated that CD4+CD25+ regulatory T cells played an important role in the process of PCV2 persistent infection.