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Reconstitution of functional status of cytotoxic T lymphocyte in chronic infection of hepatitis B virus by mimogen
Author(s) -
Wu Yuzhang
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.4
Subject(s) - cytotoxic t cell , immunology , hepatitis b virus , chronic infection , immune system , ctl* , virology , cd8 , biology , medicine , virus , in vitro , biochemistry
Cytotoxic CD8 + T lymphocytes (CTL) play a crucial role in controlling both viral replication and liver damage. We recently showed that HBV‐specific CTLs could be easily detected in peripheral blood of active chronic HBV infections. However, those results suggested that the existence of HBV‐specific CTLs were not directly correlated to hepatocyte injury, and the frequencies of HBV‐specific T cells were not determinant of immune‐mediated protection in chronic HBV infection. We now report that the detailed analysis of the function and differentiation state of epitope‐specific CTLs in chronic HBV infections by using tetramers combined intracellular cytokine staining (ICCS) and phenotypic markers. We found that HBV‐specific CTLs were skewed to an early central memory phenotype, were enriched for CD27 + /CD28 +/− expressing cells with low levels of perforin and IFN‐γ, reflecting an early intermediate stage of differentiation. Our results suggested that failure immune control in human HBV viral infection might be a result of impaired CTLs maturation into fully differentiated effector T cells. In Phase IIa clinical trial by using mimogen‐based therapeutic vaccine, We found the mimogen could upregulate the the CTLs frequency and drive the impaired functional status to functional status.