Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals

Fang Wang, Kun Yao, Quan Zhang Yin, Feng Zhou, Chuan Lin Ding, Guang Yong Peng, Jian Xu, Yun Chen, Dong Ju Feng, Chun Lin Ma, Wen Rong Xu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Human herpesvirus-6 (HHV-6) infection normally persists for the lifetime of the host and may reactivate with immunosuppression. The mechanism behind HHV-6 latent infection is still not fully understood. In this study, we observed that decreased proliferation of CD4+ T cells and PBMCs but not CD8 + T cells from HHV-6-infected individuals was stimulated with HHV-6-infected cell lysates. Moreover, HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals have suppressive activity on naive CD4 + T and CD8+ T cells from HHV-6-uninfected individuals. However, no increased proportion of CD4+ CD25+ Treg cells from HHV-6-infected individuals contributed to the suppressive activity of the HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals. Transwell experiments, ELISA and anti-IL-10 antibody blocking experiment demonstrated that IL-10 may be the suppressive cytokine required for suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interleukin (IL)-10 and IL-4 further implicated the HHV-6-specific IL-10-producing CD4+ T cells in the suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interferon (IFN)-γ demonstrated a decreased frequency of HHV-6-specific IFN-γ-producing CD4+ T, but not CD8+ T cells in HHV-6-infected individuals, indicating that it was the CD4 + Th1 responses in HHV-6-infected individuals that were selectively impaired. Our findings indicated that HHV-6-specific IL-10-producing CD4 + T cells from HHV-6-infected individuals possess T regulatory type 1 cell activity: immunosuppression, high levels of IL-10 production, with a few cells expressing IFN-γ, but none expressing IL-4. These cells may play an important role in latent HHV-6 infection.

Original languageEnglish
Pages (from-to)787-803
Number of pages17
JournalMicrobiology and Immunology
Volume50
Issue number10
DOIs
StatePublished - 2006

Keywords

  • Cell response
  • Human herpesvirus-6
  • Interleukin-10
  • T regulatory type 1 cell

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