Impaired CD4+T cell differentiation in HIV-1 infected patients receiving early anti-retroviral therapy

被引：4

作者：

Petkov, Stefan ^{[1
]}

Chiodi, Francesca ^{[1
,2
]}

机构：

[1] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Biomedicum, Solna, Sweden

[2] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Biomedicum, Solnavagen 9, S-17165 Solna, Sweden

来源：

GENOMICS | 2022年 / 114卷 / 03期

基金：

瑞典研究理事会;

关键词：

HIV-1; Early ART; RNA-seq; CD4+T cell differentiation; Transcription factors; Chemokine receptors; CD4+Th signatures; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; IMMUNE ACTIVATION; HIV-1; REPLICATION; TH22; CELLS; INFECTION; SUPPRESSION; LYMPHOCYTES; CHEMOKINES; EXPRESSION;

D O I：

10.1016/j.ygeno.2022.110367

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Differentiation of CD4+ T naive (TN) into central memory (TCM) cells involves extensive molecular processes. We compared the transcriptomes of CD4+ TN and TCM cells from HIV-1 infected patients receiving early antiretroviral therapy (ART; EA; n = 13) and controls (n = 15). Comparison of protein coding genes between TCM and TN revealed 533 and 82 differentially expressed genes (DEGs) in controls and EA, respectively. A high degree of transcriptional complexity was detected during transition of CD4+ T-N to T-CM cells in controls involving 70 TFs, 20 master regulators of T cell differentiation (TBX21, GATA3, RARA, FOXP3, RORC); in EA only 7 TFs were modulated with expression of several master regulators remaining unchanged during differentiation. Analysis of interactions between modulated TFs and target genes revealed important regulatory interactions missing in EA group. We conclude that T cell differentiation in EA patients is impaired due to reduced modulation of genes involved in transition from CD4+ TN to TCM cells.

引用

页数：15

共 80 条

[1] Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens [J].

Aandahl, EM ;

Michaëlsson, J ;

Moretto, WJ ;

Hecht, FA ;

Nixon, DF .

JOURNAL OF VIROLOGY, 2004, 78 (05) :2454-2459

[2] Transcription Factor Bcl11b controls effector and Memory CD8 T cell Fate Decision and Function during Poxvirus infection [J].

Abboud, Georges ;

Stanfield, Jessica ;

Tahiliani, Vikas ;

Desai, Pritesh ;

Hutchinson, Tarun E. ;

Lorentsen, Kyle J. ;

Cho, Jonathan J. ;

Avram, Dorina ;

Salek-Ardakani, Shahram .

FRONTIERS IN IMMUNOLOGY, 2016, 7

[3] TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection [J].

Alfei, Francesca ;

Kanev, Kristiyan ;

Hofmann, Maike ;

Wu, Ming ;

Ghoneim, Hazem E. ;

Roelli, Patrick ;

Utzschneider, Daniel T. ;

von Hoesslin, Madlaina ;

Cullen, Jolie G. ;

Fan, Yiping ;

Eisenberg, Vasyl ;

Wohlleber, Dirk ;

Steiger, Katja ;

Merkler, Doron ;

Delorenzi, Mauro ;

Knolle, Percy A. ;

Cohen, Cyrille J. ;

Thimme, Robert ;

Youngblood, Benjamin ;

Zehn, Dietmar .

NATURE, 2019, 571 (7764) :265-+

[4] Dysfunctional phenotypes of CD4+and CD8+T cells are comparable in patients initiating ART during early or chronic HIV-1 infection [J].

Amu, Sylvie ;

Graham, Rebecka Lantto ;

Bekele, Yonas ;

Nasi, Aikaterini ;

Bengtsson, Carina ;

Rethi, Bence ;

Sorial, Sam ;

Meini, Genny ;

Zazzi, Maurizio ;

Hejdeman, Bo ;

Chiodi, Francesca .

MEDICINE, 2016, 95 (23)

[5] Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART [J].

Bacchus-Souffan, Charline ;

Fitch, Mark ;

Symons, Jori ;

Abdel-Mohsen, Mohamed ;

Reeves, Daniel B. ;

Hoh, Rebecca ;

Stone, Mars ;

Hiatt, Joseph ;

Kim, Peggy ;

Chopra, Abha ;

Ahn, Haelee ;

York, Vanessa A. ;

Cameron, Daniel L. ;

Hecht, Frederick M. ;

Martin, Jeffrey N. ;

Yukl, Steven A. ;

Mallal, Simon ;

Cameron, Paul U. ;

Deeks, Steven G. ;

Schiffer, Joshua T. ;

Lewin, Sharon R. ;

Hellerstein, Marc K. ;

McCune, Joseph M. ;

Hunt, Peter W. .

PLOS PATHOGENS, 2021, 17 (01)

[6] Mechanisms of HIV-associated lymphocyte apoptosis [J].

Badley, AD ;

Pilon, AA ;

Landay, A ;

Lynch, DH .

BLOOD, 2000, 96 (09) :2951-2964

[7] CCR8+FOXp3+ Treg cells as master drivers of immune regulation [J].

Barsheshet, Yiftah ;

Wildbaum, Gizi ;

Levy, Eran ;

Vitenshtein, Alon ;

Akinseye, Chika ;

Griggs, Jeremy ;

Lira, Sergio A. ;

Karin, Nathan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (23) :6086-6091

[8] Predicting tissue-specific gene expression from whole blood transcriptome [J].

Basu, Mahashweta ;

Wang, Kun ;

Ruppin, Eytan ;

Hannenhalli, Sridhar .

SCIENCE ADVANCES, 2021, 7 (14)

[9] Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation [J].

Bekele, Yonas ;

Lakshmikanth, Tadepally ;

Chen, Yang ;

Mikes, Jaromir ;

Nasi, Aikaterini ;

Petkov, Stefan ;

Hejdeman, Bo ;

Brodin, Petter ;

Chiodi, Francesca .

JCI INSIGHT, 2019, 4 (03)

[10] MiXCR: software for comprehensive adaptive immunity profiling [J].

Bolotin, Dmitriy A. ;

Poslavsky, Stanislav ;

Mitrophanov, Igor ;

Shugay, Mikhail ;

Mamedov, Ilgar Z. ;

Putintseva, Ekaterina V. ;

Chudakov, Dmitriy M. .

NATURE METHODS, 2015, 12 (05) :380-381

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