HIV-Specific CD8 T Cells Producing CCL-4 Are Associated with Worse Immune Reconstitution during Chronic Infection

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Abstract

Background: Immunological nonresponse represents the Achilles heel in the combination antiretroviral therapy (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication, and polyfunctional HIV-specific CD8 T cells have been associated with nonprogressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting posttreatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients. Methods: A cohort of chronic HIV-infected individuals naive to cART were enrolled in the ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as susceptibility to apoptosis were analyzed before and after 12 months of cART. Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was also assessed. Results: Results showed a significant correlation between worse CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells all before cART. Moreover, CD8 functional subsets expressing total C-C motif chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma (IFNγ) were negatively associated with immune reconstitution. Conclusions: In conclusion, our study shows that a more differentiated phenotype of CD4 T cells and CCL-4-producing CD8 T cells could represent valuable predictors of worse immune reconstitution. These parameters may be used as tools for identifying patients at risk of immunological failure during cART and eventually represent the basis for innovative therapeutic strategies.

Original languageEnglish
Pages (from-to)338-344
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume75
Issue number3
DOIs
Publication statusPublished - Jul 1 2017

Fingerprint

C Chemokines
HIV
Ligands
T-Lymphocytes
Infection
Therapeutics
Apoptosis
CC Chemokines
T-Lymphocyte Subsets
Interferon-gamma
HIV Infections

Keywords

  • CCL-4
  • CD8 T-cell response
  • HIV infection
  • immunological non response
  • polyfunctionality
  • prognostic factors

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

@article{8c68b907e61f45a4989fab12da57fee1,
title = "HIV-Specific CD8 T Cells Producing CCL-4 Are Associated with Worse Immune Reconstitution during Chronic Infection",
abstract = "Background: Immunological nonresponse represents the Achilles heel in the combination antiretroviral therapy (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication, and polyfunctional HIV-specific CD8 T cells have been associated with nonprogressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting posttreatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients. Methods: A cohort of chronic HIV-infected individuals naive to cART were enrolled in the ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as susceptibility to apoptosis were analyzed before and after 12 months of cART. Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was also assessed. Results: Results showed a significant correlation between worse CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells all before cART. Moreover, CD8 functional subsets expressing total C-C motif chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma (IFNγ) were negatively associated with immune reconstitution. Conclusions: In conclusion, our study shows that a more differentiated phenotype of CD4 T cells and CCL-4-producing CD8 T cells could represent valuable predictors of worse immune reconstitution. These parameters may be used as tools for identifying patients at risk of immunological failure during cART and eventually represent the basis for innovative therapeutic strategies.",
keywords = "CCL-4, CD8 T-cell response, HIV infection, immunological non response, polyfunctionality, prognostic factors",
author = "Rita Casetti and Carmela Pinnetti and Alessandra Sacchi and {De Simone}, Gabriele and Veronica Bordoni and Eleonora Cimini and Nicola Tumino and Francesca Besi and Domenico Viola and Federica Turchi and Valentina Mazzotta and Andrea Antinori and Federico Martini and Adriana Ammassari and Chiara Agrati",
year = "2017",
month = "7",
day = "1",
doi = "10.1097/QAI.0000000000001392",
language = "English",
volume = "75",
pages = "338--344",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - HIV-Specific CD8 T Cells Producing CCL-4 Are Associated with Worse Immune Reconstitution during Chronic Infection

AU - Casetti, Rita

AU - Pinnetti, Carmela

AU - Sacchi, Alessandra

AU - De Simone, Gabriele

AU - Bordoni, Veronica

AU - Cimini, Eleonora

AU - Tumino, Nicola

AU - Besi, Francesca

AU - Viola, Domenico

AU - Turchi, Federica

AU - Mazzotta, Valentina

AU - Antinori, Andrea

AU - Martini, Federico

AU - Ammassari, Adriana

AU - Agrati, Chiara

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background: Immunological nonresponse represents the Achilles heel in the combination antiretroviral therapy (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication, and polyfunctional HIV-specific CD8 T cells have been associated with nonprogressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting posttreatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients. Methods: A cohort of chronic HIV-infected individuals naive to cART were enrolled in the ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as susceptibility to apoptosis were analyzed before and after 12 months of cART. Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was also assessed. Results: Results showed a significant correlation between worse CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells all before cART. Moreover, CD8 functional subsets expressing total C-C motif chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma (IFNγ) were negatively associated with immune reconstitution. Conclusions: In conclusion, our study shows that a more differentiated phenotype of CD4 T cells and CCL-4-producing CD8 T cells could represent valuable predictors of worse immune reconstitution. These parameters may be used as tools for identifying patients at risk of immunological failure during cART and eventually represent the basis for innovative therapeutic strategies.

AB - Background: Immunological nonresponse represents the Achilles heel in the combination antiretroviral therapy (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication, and polyfunctional HIV-specific CD8 T cells have been associated with nonprogressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting posttreatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients. Methods: A cohort of chronic HIV-infected individuals naive to cART were enrolled in the ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as susceptibility to apoptosis were analyzed before and after 12 months of cART. Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was also assessed. Results: Results showed a significant correlation between worse CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells all before cART. Moreover, CD8 functional subsets expressing total C-C motif chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma (IFNγ) were negatively associated with immune reconstitution. Conclusions: In conclusion, our study shows that a more differentiated phenotype of CD4 T cells and CCL-4-producing CD8 T cells could represent valuable predictors of worse immune reconstitution. These parameters may be used as tools for identifying patients at risk of immunological failure during cART and eventually represent the basis for innovative therapeutic strategies.

KW - CCL-4

KW - CD8 T-cell response

KW - HIV infection

KW - immunological non response

KW - polyfunctionality

KW - prognostic factors

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U2 - 10.1097/QAI.0000000000001392

DO - 10.1097/QAI.0000000000001392

M3 - Article

C2 - 28418988

AN - SCOPUS:85017619469

VL - 75

SP - 338

EP - 344

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 3

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