Profiles of cytokines produced by CD4-positive T lymphocytes stimulated by anti-CD3 antibody in patients with chronic hepatitis C.
Helper T cells (Th) are classified as type 1 (Th1) and type 2 (Th2) according to the cytokines they produce; interferon-gamma is produced by Th1, and interleukin-4 by Th2. We counted the circulating CD4-positive Th cells that produce interferon-gamma or interleukin-4 with an enzyme-linked immunospot assay. CD4-positive T cells isolated from patients with chronic hepatitis B (n = 10), chronic hepatitis C (n = 16), and healthy subjects (n = 10) were stimulated with anti-CD3 antibody in vitro. The number of interferon-gamma-producing Th cells was significantly lower in patients with chronic hepatitis C than in healthy subjects (P = 0.0024), whereas in patients with chronic hepatitis B, the number was similar to that in healthy subjects (P = 0.8530). The number of interleukin-4-producing Th cells was significantly higher in patients with chronic hepatitis C (P = 0.0010) and chronic hepatitis B (P = 0.0089) than in healthy subjects. In chronic hepatitis C, the number of interferon-gamma-producing Th cells was increased after incubation of the cells with interferon-alpha (P = 0.008) or with recombinant interferon-gammala (P = 0.024), but not with interferon-beta (P = 0.051). The number of interleukin-4-producing Th cells was decreased after incubation with interferon-alpha (P = 0.0004), with interferon-beta (P = 0.003), and with recombinant interferon-gammala (P = 0.0004). Changes in the numbers of interferon-gamma- or interleukin-4-producing Th cells in vitro were more evident in sustained responders to interferon therapy than in non-responders. These results suggest that Th2 cells are the predominant cell type in chronic hepatitis C, and that their activity may be suppressed by the administration of interferon.
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
K
K
Kobayashi
M
M
Ishii
T
T
Igarashi
T
T
Satoh
Y
Y
Miyazaki
Y
Y
Yajima
K
K
Ukai
H
H
Suzuki
A
A
Kanno
Y
Y
Ueno
T
T
Miura
T
T
Toyota
D000328:Adult; D044466:Asian People; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012194:RNA-Directed DNA Polymerase
D017252:CD3 Complex; D017931:DNA Primers; D015847:Interleukin-4; D007371:Interferon-gamma; D012194:RNA-Directed DNA Polymerase