TCD8 response in diverse outcomes of recurrent exposure to hepatitis C virus.
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-gamma (IFNgamma) 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 IFNgamma and tumour-necrosis factor-alpha, 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.
Bharadwaj
Mandvi
M
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia. mandvi@unimelb.edu.au
Thammanichanond
Duangtawan
D
Aitken
Campbell Kynoch
CK
Moneer
Sarah
S
Drummer
Heidi E
HE
Tracy
Samantha
S
Holdsworth
Rhonda
R
Bowden
Scott
S
Jackson
David
D
Hellard
Margaret
M
Torresi
Joseph
J
McCluskey
James
J
D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D055030:Drug Users; D004781:Environmental Exposure; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012075:Remission, Spontaneous; D055502:Secondary Prevention; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma