title: Low Double-Negative CD3+CD4-CD8-T Cells Are Associated with Incomplete Restoration of CD4+T Cells and Higher Immune Activation in HIV-1 Immunological Non-Responders.
abstract: Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3+CD4-CD8-T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4+T cell count. The ART did not result in complete suppression of immune activation recorded by the percentage of CD38+HLA-DR+CD8+T cells in INRs, and a strong inverse correlation was observed between DN T cells and immune activation. A low proportion of TGF-β1+DN T cells was found in INRs. Further mechanism study demonstrated that the level of TGF-β1-producing DN T cells and immune activation had a negative correlation after ART. Taken together, our study suggests that DN T cells control the immunological response in HIV-1-infected patients. These findings expand our understanding of the mechanism of immune reconstitution and could develop specific treatments to return the immune system to homeostasis following initiation of HIV-1 therapy.
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Lu
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xia
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ji
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University , Beijing , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Dai
authors.affiliation: INSERM UMR S_1109, Faculté de Médecine, FMTS, Centre de Recherche en Immunologie et Hématologie, Université de Strasbourg , Strasbourg , France.
authors.forename: Luzia M
authors.initials: LM
authors.lastname: Mayr
authors.affiliation: INSERM UMR S_1109, Faculté de Médecine, FMTS, Centre de Recherche en Immunologie et Hématologie, Université de Strasbourg , Strasbourg , France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University , Beijing , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University , Beijing , China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Huang
authors.affiliation: STD/HIV Research Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory for HIV/AIDS Research, Beijing, China; Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
keywords: HIV-1; TGF-β1; antiretroviral therapy; double-negative T cell; immune activation; immune reconstitution