Dissecting the role of TGF-beta+ regulatory CD4+ T cells in pathogenesis of Marek's disease in chickens

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White blood cells are a key part of the body's immune system to combat infections by viruses, bacteria and other pathogens. Our research is focused on a type of white blood cells called T cells. There are different types of T cells with distinct functional abilities, for example, killer T cells recognize and lyse cancer cells or infected cells, while suppressor T cells dampen immunity and suppress inflammatory responses. Many pathogens have learned to co-exist with the host by manipulating suppressor T cells to their advantage and thus they can escape immune control. We know very little about suppressor T cells in chicken, because we do not have specific and stable markers to identify these cells in chickens. A novel chicken suppressor T cell subpopulation has been recently identified, by our group, based on the expression of a suppressive molecule called TGF-beta. We have demonstrated that these cells may be involved in the pathogenesis of an economically important infectious disease called "Marek's disease" in chickens. Similar to humans, many animals including chickens develop cancer with the distinction that cancers in animals are mainly induced by viruses. Marek's disease (MD) is a common disease of chickens, causing transformation of the infected T cells and tumour growth in various tissues and eventually death. Our data show that cancer cells resemble the recently identified suppressor T cells and Marek disease infection increases the number of the suppressor T cells in the birds. We propose to determine whether the recently identified suppressor T cells are the precursor of cancer cells and if these cells are specifically targeted by the virus. We will also explore whether differences in molecular signature of the recently identified suppressor T cells can explain the susceptibility to MDV infection.