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Immune response of host to virus infections, emphasizing cellular responses
- Human Immune Responses
- Immunopathology to Virus Infections and
- Failure to Eliminate Virus in Persistent Infection
A. T cell triggered and cytokine mediated immunopathology.
We hypothesize that certain virus infections e.g. Dengue HemorrhagicFever (DHF), or the Hantavirus Pulmonary Syndrome (HPS) may be due to"over"responses of dengue or hantavirus specific T cells incertain high-responders, due to immune responses genes. These T cellresponses are needed for clearance of virus-infected cells but markedinflammatory responses probably mediated by cytokines, cause endothelialcell leakness and shock (DHF) or pulmonary edema (HPS). We are definingCD4+ and CD8+ T cell epitopes, determining the Th1 and Th2 cytokineresponses at the protein and m-RNA levels and by immunocytochemistry. TCRusage is determined, and correlations with disease phenotypes arestudied.
Immunopathogenesis of DHF
B. Failure to Eliminate Virus in HCV Infection
Failure of immune response to eliminate HCV infection is very commonand chronic progression liver disease frequently results. Is this due toa poor CD8+ T cell response in those individuals? We are also developingCD8+ T cell clones from the liver tissues and blood cells of patients withHCV infections. We will determine whether interferon therapy which is theonly known treatment, alters the HCV+ CD8+ CTL responses in the patientswho respond to therapy or those that do not. We are also defining Th1,Th2 cytokine patterns in liver tissues by immunocytochemistry.
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