Spontaneous recovery in acute human hepatitis C virus infection: functional T-cell thresholds and relative importance of CD4 help.
The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection are incompletely understood because early infection in humans is rarely identified, particularly in those individuals who subsequently demonstrate spontaneous virus eradication. We have established a large national network of patients with acute HCV infection. Here, we comprehensively examined total HCV-specific CD4(+) and CD8(+) T-cell responses and identified functional T-cell thresholds that predict recovery. Interestingly, we found that the presence of HCV-specific cytotoxic T lymphocytes (CTLs) that can proliferate, exhibit cytotoxicity, and produce gamma interferon does not ensure recovery, but whether these CTLs were primed in the presence or absence of CD4(+) T-cell help (HCV-specific interleukin-2 production) is a critical determinant. These results have important implications for early prediction of the virologic outcome following acute HCV and for the development of novel immunotherapeutic approaches.
Smyk-Pearson
Susan
S
GI and Hepatology Division, B-158, Academic Office Building 1, 12631 East 17th Ave., Room 7614, P.O. Box 6511, Aurora, CO 80045, USA.
Tester
Ian A
IA
Klarquist
Jared
J
Palmer
Brent E
BE
Pawlotsky
Jean-Michel
JM
Golden-Mason
Lucy
L
Rosen
Hugo R
HR
D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003289:Convalescence; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D012075:Remission, Spontaneous; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D007371:Interferon-gamma