FOXP3 expression in hepatitis C virus-specific CD4+ T cells during acute hepatitis C.
OBJECTIVE
Down-regulation of hepatitis C virus (HCV)-specific CD4(+) T-cell responses is a hallmark of chronic viral persistence in acute hepatitis C. FOXP3(+)CD25(+)CD4(+) regulatory T cells can modulate HCV-specific immune responses in vitro, but the role of virus-specific regulatory T cells in the pathogenesis of chronic viral persistence is unknown.


METHODS
Two novel HLA-DR15 tetramers were synthesized to study the kinetics and phenotype of FOXP3(+)-expressing HCV-specific CD4(+) T cells from 10 patients with acute hepatitis C and 15 patients with chronic hepatitis C.


RESULTS
In acute hepatitis C, generally only a low percentage of HCV-specific CD4(+) T cells expressed FOXP3(+) (mean of 2.5% in patients with self-limited acute hepatitis C vs 2.4% in patients with evolving chronic hepatitis C). Although distinct but short-lived increases in virus-specific FOXP3(+)CD4(+) T cells occurred in 3 patients (30%, 26%, and 7% of tet(+) CD4(+) T cells, respectively), these did not correlate with the evolution of chronic hepatitis C. HCV-specific FOXP3(+)CD4(+) T cells displayed a distinct phenotype, with only 10% expressing CD25 and 40% being CD127low. Interestingly, this phenotype of FOXP3(+)CD4(+) T cells was already expanded in bulk CD4(+) T cells in patients with chronic hepatitis C.


CONCLUSIONS
Although short-lived increases in HCV-specific FOXP3(+)CD4(+) T cells occur during the course of acute hepatitis C, we could not demonstrate an association of HCV-specific regulatory T cells and persistent viremia.
Heeg
Malte H J
MH
Medical Department II and Institute for Immunology, Ludwig-Maximilians-University Munich, Munich, Germany.
Ulsenheimer
Axel
A
Grüner
Norbert H
NH
Zachoval
Reinhart
R
Jung
Maria-Christina
MC
Gerlach
J Tilman
JT
Raziorrouh
Bijan
B
Schraut
Winfried
W
Horster
Sophia
S
Kauke
Teresa
T
Spannagl
Michael
M
Diepolder
Helmut M
HM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D014766:Viremia / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D018937:Hepatitis C Antibodies; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit