Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals.
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 naïve 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)-gamma demonstrated a decreased frequency of HHV-6-specific IFN-gamma-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-gamma, but none expressing IL-4. These cells may play an important role in latent HHV-6 infection.
Wang
Fang
F
Department of Microbiology and Immunology, NanJing Medical University, 140 Han Zhong Road, Nanjing 210029, Jiangsu, P.R. China.
Yao
Kun
K
Yin
Quan-Zhang
QZ
Zhou
Feng
F
Ding
Chuan-Lin
CL
Peng
Guang-Yong
GY
Xu
Jian
J
Chen
Yun
Y
Feng
Dong-Ju
DJ
Ma
Chun-Lin
CL
Xu
Wen-Rong
WR
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D019349:Roseolovirus Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma