Depletion of CD25 + CD4 + T cells (Tregs) enhances the HBV-specific CD8 + T cell response primed by DNA immunization

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 24; pp. 3772 - 3777
• Main Author: Furuichi, Yoshihiro
• Format: Journal Article
• Language: English
• Published: United States Fourth Department of Internal Medicine (Gastroenterology and Hepatology), Tokyo Medical University, Tokyo, Japan%Department of Molecular and Preventive Medicine, Graduate School of Medicine, University of Tokyo,Tokyo, Japan%Department of Immunotherapeutics (Medinet), Graduate School of Medicine, University of Tokyo,Tokyo, Japan 28.06.2005; Baishideng Publishing Group Inc
• Subjects: Animals; Brief Reports; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - virology; DNA, Viral - immunology; Hepatitis B Vaccines - pharmacology; Hepatitis B virus - immunology; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - therapy; Immunization; Male; Mice; Mice, Inbred Strains; Receptors, Interleukin-2 - metabolism; Regulatory T cell (Treg); Vaccine; Hepatitis B virus; DNA immunization; Cytotoxic T lymphocyte
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v11.i24.3772

Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8(+) T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25(+)CD4(+) regulatory T (Treg) cells might be involved in a inhibition of CD8(+) T cell priming or in the modulation of the magnitude of the 'peak' antiviral CD8(+) T cell response primed by DNA immunization. B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 microg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25(+) cells. Induction of HBV-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-gamma staining. DNA immunization induced HBV-specific CD8(+) T cells. At the peak T cell response (d 10), 7.1+/-2.0% of CD8(+) T cells were HBV-specific after DNA immunization, whereas 12.7+/-3.2% of CD8(+) T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8(+) T cells in the absence of CD25(+) Treg cells (n = 6, P<0.05). Similarly, fewer HBV-specific memory T cells were detected in the presence of these cells (1.3+/-0.4%) in comparison to Treg-depleted mice (2.6+/-0.9%) on d 30 after DNA immunization (n = 6, P<0.01). Both IFN-gamma production and the avidity of the HBV-specific CD8(+) T cell response to antigen were higher in HBV-specific CD8(+) T cells induced in the absence of Treg cells. CD25(+) Treg cells suppress priming and/or expansion of antigen-specific CD8(+) T cells during DNA immunization and the peak CD8(+) T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8(+) T cell response and may affect the quality of memory T cell pools. The elimination of Treg cells or their inhibition may be important in immunotherapeutic strategies to control HBV infection by inducing virus-specific cytotoxic T lymphocyte responses in chronically infected subjects.