[CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection].
OBJECTIVE
To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+) CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent infection of hepatitis C viruses.


METHODS
Flow cytometry was used to determine the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of Foxp3 were measured by RT-PCR.


RESULTS
CD(4)(+) CD(25)(+) Treg cells comprised (13.5 +/- 1.8)% of peripheral CD(4)(+) T cells in the blood of persistent hepatitis C virus infected patients, which was significantly higher than that of healthy controls (5.3 +/- 0.8)% (P = 0.004). CD(4)(+) CD(25)(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells dramatically suppressed the proliferation of CD(4)(+) T cells and the production of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) Treg cells in patients with persistent HCV-infection was higher than that in healthy controls (P = 0.034). These effects were dose-dependent but IL-10 and transforming growth factor beta independent.


CONCLUSIONS
Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+) Treg cells, which could function in a highly regulatory capacity to suppress Th1 response.
Yang
Jiang-hua
JH
Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhang
Yong-xiang
YX
Yu
Rong-bin
RB
Su
Chuan
C
Sun
Nan-xiong
NX
D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2