T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection.

Abstract

Chronic hepatitis C virus (HCV) infection is associated with impaired proliferative, cytokine, and cytotoxic effector functions of HCV-specific CD8(+) T cells that probably contribute significantly to viral persistence. Here, we investigated the potential role of T cells with a CD4(+)CD25(+) regulatory phenotype in suppressing virus-specific CD8(+) T-cell proliferation during chronic HCV infection. In vitro depletion studies and coculture experiments revealed that peptide specific proliferation as well as gamma interferon production of HCV-specific CD8(+) T cells were inhibited by CD4(+)CD25(+) T cells. This inhibition was dose dependent, required direct cell-cell contact, and was independent of interleukin-10 and transforming growth factor beta. Interestingly, the T-cell-mediated suppression in chronically HCV-infected patients was not restricted to HCV-specific CD8(+) T cells but also to influenza virus-specific CD8(+) T cells. Importantly, CD4(+)CD25(+) T cells from persons recovered from HCV infection and from healthy blood donors exhibited significantly less suppressor activity. Thus, the inhibition of virus-specific CD8(+) T-cell proliferation was enhanced in chronically HCV-infected patients. This was associated with a higher frequency of circulating CD4(+)CD25(+) cells observed in this patient group. Taken together, our results suggest that chronic HCV infection leads to the expansion of CD4(+)CD25(+) T cells that are able to suppress CD8(+) T-cell responses to different viral antigens. Our results further suggest that CD4(+)CD25(+) T cells may contribute to viral persistence in chronically HCV-infected patients and may be a target for immunotherapy of chronic hepatitis C.

• Authors: Tobias Boettler, Hans Christian Spangenberg, Christoph Neumann-Haefelin, Elisabeth Panther, Simonetta Urbani, Carlo Ferrari, Hubert E Blum, Fritz von Weizsäcker, Robert Thimme
• Journal: Journal of virology (J Virol) Vol. 79 Issue 12 Pg. 7860-7 (Jun 2005) ISSN: 0022-538X [Print] United States
• PMID: 15919940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• Receptors, Interleukin-2

Topics

• Adult
• Amino Acid Sequence
• CD4 Antigens (metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Communication
• Female
• Hepacivirus
• Hepatitis C, Chronic (immunology)
• Humans
• Lymphocyte Activation (immunology)
• Male
• Middle Aged
• Molecular Sequence Data
• Phenotype
• Receptors, Interleukin-2 (metabolism)
• T-Lymphocytes, Regulatory (immunology)