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For the past few years specific regulatory T lym-phocytes including double negative T cells (DN Treg cells), CD4+CD25+ T cells and CD4+cytotoxic T lymphocytes have been the focus of immunological studies due to their roles in the development of many diseases. DN Treg cell, a recently identified regulatory T lymphocyte whose surface marker is TCRαβ+CD4-CD8-CD25+CD28-CD30+CD44-, shows specific cyto-toxic effects on syngeneic MHC-antigen complex CD8+ T cells through Fas/FasL interaction and extended graft survival time after activation (18). CD4+CD25+ T cells whose surface marker is TCRαβ+ CD3+CD4+ CD25+ CD45RO+ CTLA-4+could inhibit internal and external antigen induced immune responses after activation through the mechanism of inhibition cytokines and cell-cell contact (1, 5, 6, 10, 12), and thus plays an important role in the pathogenesis of infection, oncosis and autoimmune diseases (3, 7, 9).
Recent studies showed that in the process of viral infection, induced tissue damage and virus clearing, T lymphocyte plays an important role (3, 9). Virus hepatitis is a process of immunity induced hepatocyte inflammation damage. Until now, the understanding of Virus hepatitis immunopathogenesis remains at the level of CD8+ cytotoxic T lymphocytes (CTL). Further studies of the modulation factor of CD8+ CTL still are inconclusive. Qin et al constructed a C3H/Hej mouse chronic viral hepatitis model in which C3H/Hej mice individually received 10 PFU MHV-3 intra-peritoneally (8). In this study, we observed the changes of virus titer and pathology in livers of the C3H/Hej mouse chronic viral hepatitis model. Then we observed the ratios of T cell subsets of total T lymphocytes including the ratios of CD3+CD4-CD8-, CD3+CD4+CD8-CD3+CD4-CD8+, CD3+CD4+ CD25+T cell in the models.
A Primary Study of the Subgroups of T Lymphocytes in MHV-3 Induced Chronic Viral Hepatitis*
- Received Date: 21 April 2007
- Accepted Date: 18 June 2007
Abstract: To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type 3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units(PFU)of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+ CD4-CD25+ T lymphocyte of 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. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 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. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice. The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.