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T CD8 response in diverse outcomes of recurrent exposure to hepatitis C virus
Author(s) -
Bharadwaj Mandvi,
Thammanichad Duangtawan,
Aitken Campbell Kynoch,
Moneer Sarah,
Drummer Heidi E,
Tracy Samantha,
Holdsworth Rhonda,
Bowden Scott,
Jackson David,
Hellard Margaret,
Torresi Joseph,
McCluskey James
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.24
Subject(s) - elispot , cytotoxic t cell , immunology , ex vivo , cd8 , hepatitis c virus , immune system , virology , hepatitis c , medicine , biology , in vivo , virus , in vitro , biochemistry , microbiology and biotechnology
To analyse the immune correlates in a setting of recurrent exposure to hepatitis C virus (HCV), we studied T CD8 responses in injecting drug users (IDUs) with different disease outcomes. Ex vivo HCV‐specific T CD8 responses assessed by interferon‐γ (IFNγ) enzyme‐linked immunospot (ELISPOT) were comparable in human lymphocyte antigen (HLA)‐matched IDUs with spontaneous HCV clearance or persistent infection. A detailed characterization of these T CD8 cells in age and HLA‐matched IDUs demonstrated that HCV clearance and protection from reinfection correlated with HCV‐specific T CD8 cells that could proliferate in vitro , possessed cytotoxic potential and produced IFNγ and tumour‐necrosis factor‐α, rather than with the circulating frequency of responding T CD8 cells determined ex vivo . While validating the importance of multifunctional T CD8 in mediating protection in IDUs with recurrent exposure to HCV our findings highlight that the magnitude and/or breadth of HCV‐specific T CD8 determined in ex vivo ELISPOT may not be the sole determinant of protection especially in a setting of recurrent exposure.