Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children.
Anti-Retroviral Agents
/ therapeutic use
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ physiology
Cell Proliferation
Child
Child, Preschool
Cytokines
/ metabolism
Cytomegalovirus
/ immunology
Female
HIV
/ immunology
HIV Infections
/ drug therapy
Humans
Immune Reconstitution
Immunologic Memory
Lymphocyte Activation
Male
Mycobacterium tuberculosis
/ immunology
Phenotype
Programmed Cell Death 1 Receptor
/ metabolism
Prospective Studies
HIV
antiretroviral therapy
cytomegalovirus
tuberculosis
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
16 04 2019
16 04 2019
Historique:
received:
17
07
2018
accepted:
19
12
2018
pubmed:
10
1
2019
medline:
10
1
2020
entrez:
10
1
2019
Statut:
ppublish
Résumé
Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART. We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation. We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution.
Sections du résumé
BACKGROUND
Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART.
METHODS
We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation.
RESULTS
We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively).
CONCLUSIONS
Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution.
Identifiants
pubmed: 30624717
pii: 5280900
doi: 10.1093/infdis/jiy668
pmc: PMC6467189
doi:
Substances chimiques
Anti-Retroviral Agents
0
Cytokines
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1417Subventions
Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : Wellcome Trust
ID : WT104748MA
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
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