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2030-01-01
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- IOC - Artigos de Periódicos [12364]
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PHENOTYPE AND FUNCTION OF HBV-SPECIFIC T CELLS IS DETERMINED BY THE TARGETED EPITOPE IN ADDITION TO THE STAGE OF INFECTION
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Abstract
Objective Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack
curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence
indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional
cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control. Design The phenotype and function of HBVspecific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection. Results We detected strong T cell responses targeting multiple HBV viral proteins in acute selflimiting and low-frequency core and polymerasespecific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly
between T cells targeting different HBV specificities. Conclusion HBV-specific T cells with different target specificities are characterised by distinct
phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are
potentially relevant for informing immunotherapeutic approaches to induce functional cure.
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