CD4~-CD8~- T Cells Contribute To The Persistence Of MHV-3 Induced Chronic Viral Hepatitis

Objective:To study the contribution of T cell subsets to the pathogenesis in MHV-3 induced chronic viral hepatitis in C3H/Hej mouse.Methods:In this work, ninety C3H/Hej mice individually received 10 plaque forming units (Pfu) of MHV-3 intraperitoneally. The ratios of T cell subsets including CD3~+CD4~+CD8-, CD3~+CD4-CD8~+,CD3~+CD4-CD8-( DNT cells), CD3~+CD4~+CD25~+, CD3~+CD4~+CD25-, CD3~+CD4- CD25~+ T lymphocytes in total T lymphocytes in blood, spleen and liver were examined at 0,2,4,6,8,10,12,15,20,25,30,40 days post MHV-3 infection by flow cytosorting. Magnetic bead sorting was applied for the purification of T cell subsets. The cytotoxic effects of DNT cells and CD4~+CD25~+T cells on both CD8~+T cells and hepatocytes were examined by CytoTox96 Non-Radioactive Cytotoxicity Assay at 0, 4, 15, 30, 40days post MHV-3 infection.Results: The DNT cell and CD4~+CD25~+T cell ratios raised significantly since 2 days post MHV-3 infection in C3H/Hej mice, and CD3~+CD4~+CD8- , CD3~+CD4-CD8~+ CD3~+CD4~+CD25- and CD3~+CD4-CD25~+ T cell ratios decreased accordingly. DNT cells showed significant cytotoxic effects on CD8~+ T cells with a cytotoxic rate of 97.00%±0.01 %, while CD4~+CD25~+T cells only had slight cytotoxic effects on it with a cytotoxic rate of 51.27%±0.01%.Conclusions:Here we first report that DNT cells, rather than CD4~+CD25~+T cells, have more profound immune modulatory effect on CD8~+T cells in MHV-3 induced chronic viral hepatitis in C3H/Hej mice, suggesting their contribution to viral persistence. Further characterizations of DNT cells are under studying.