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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

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...

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Autores principales: Lu, Xiaofan, Su, Bin, Xia, Huan, Zhang, Xin, Liu, Zhiying, Ji, Yunxia, Yang, Zixuan, Dai, Lili, Mayr, Luzia M., Moog, Christiane, Wu, Hao, Huang, Xiaojie, Zhang, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145861/
https://www.ncbi.nlm.nih.gov/pubmed/28018346
http://dx.doi.org/10.3389/fimmu.2016.00579
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author Lu, Xiaofan
Su, Bin
Xia, Huan
Zhang, Xin
Liu, Zhiying
Ji, Yunxia
Yang, Zixuan
Dai, Lili
Mayr, Luzia M.
Moog, Christiane
Wu, Hao
Huang, Xiaojie
Zhang, Tong
author_facet Lu, Xiaofan
Su, Bin
Xia, Huan
Zhang, Xin
Liu, Zhiying
Ji, Yunxia
Yang, Zixuan
Dai, Lili
Mayr, Luzia M.
Moog, Christiane
Wu, Hao
Huang, Xiaojie
Zhang, Tong
author_sort Lu, Xiaofan
collection PubMed
description 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.
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spelling pubmed-51458612016-12-23 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 Lu, Xiaofan Su, Bin Xia, Huan Zhang, Xin Liu, Zhiying Ji, Yunxia Yang, Zixuan Dai, Lili Mayr, Luzia M. Moog, Christiane Wu, Hao Huang, Xiaojie Zhang, Tong Front Immunol Immunology 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. Frontiers Media S.A. 2016-12-09 /pmc/articles/PMC5145861/ /pubmed/28018346 http://dx.doi.org/10.3389/fimmu.2016.00579 Text en Copyright © 2016 Lu, Su, Xia, Zhang, Liu, Ji, Yang, Dai, Mayr, Moog, Wu, Huang and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lu, Xiaofan
Su, Bin
Xia, Huan
Zhang, Xin
Liu, Zhiying
Ji, Yunxia
Yang, Zixuan
Dai, Lili
Mayr, Luzia M.
Moog, Christiane
Wu, Hao
Huang, Xiaojie
Zhang, Tong
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145861/
https://www.ncbi.nlm.nih.gov/pubmed/28018346
http://dx.doi.org/10.3389/fimmu.2016.00579
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