Dataset Information

Gag-Specific CD8 T-Cell Proliferation Is Associated With Higher Peripheral Blood Levels of Transforming Growth Factor-β and Gut-Homing T Cells in Youths Perinatally Infected With Human Immunodeficiency Virus-1: The ANRS-EP38-IMMIP Study.

ABSTRACT:

Background

Gag-specific T lymphocytes play a key role in the control of human immunodeficiency virus (HIV) replication. Their restoration will be important for future reservoir targeting strategies. In this study, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection.

Methods

The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking combination anti-retroviral therapy and aviremic at the time of the study and had undergone valid 5-6-carboxyfluorescein diacetate succimidyl ester-based flow cytometry T-cell proliferation assays. Plasma analytes were quantified by enzyme-linked immunosorbent assay or multiplex assays. Peripheral blood cells were phenotyped by flow cytometry. Logistic regression was used to study the association between Gag-specific T-cell proliferation and immune markers.

Results

Patients with Gag-specific CD8 T-cell proliferation had higher levels of plasma transforming growth factor (TGF)-β1, a lower proportion of naive cells among regulatory T cells (Tregs), and higher percentages of CD4 and CD8 T cells expressing the α₄β₇ integrin or CD161 molecule than those without a Gag-specific response. These associations were significant based on analyses including potential confounders.

Conclusions

Preserved Gag-specific CD8 T-cell proliferation was associated with higher TGF-β1 levels and increased percentages of T cells with a gut-homing phenotype at least 15 years after HIV infection during the perinatal period.

SUBMITTER: Warszawski J

PROVIDER: S-EPMC5414023 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gag-Specific CD8 T-Cell Proliferation Is Associated With Higher Peripheral Blood Levels of Transforming Growth Factor-β and Gut-Homing T Cells in Youths Perinatally Infected With Human Immunodeficiency Virus-1: The ANRS-EP38-IMMIP Study.

Warszawski Josiane J Avettand-Fenoel Véronique V Rouzioux Christine C Scott-Algara Daniel D Montange Thomas T Didier Céline C Le Chenadec Jérôme J Viard Jean-Paul JP Dollfus Catherine C Blanche Stéphane S Buseyne Florence F

Open forum infectious diseases 20161207 1

<h4>Background</h4>Gag-specific T lymphocytes play a key role in the control of human immunodeficiency virus (HIV) replication. Their restoration will be important for future reservoir targeting strategies. In this study, we aimed to identify immune correlates of Gag-specific CD8 T-cell proliferation in youths with perinatally acquired HIV-1 infection.<h4>Methods</h4>The ANRS-EP38-IMMIP study included youths of 15 to 24 years of age. Fifty-three were taking combination anti-retroviral therapy an ...[more]

PMID: 28480237

Similar Datasets

Project description:ObjectiveThis study assessed impaired fasting glucose and associated factors among perinatally HIV-infected adolescents and youths in Dar es salaam Tanzania.BackgroundImpaired fasting glucose is a marker of heightened risk for developing type 2 diabetes among perinatally HIV-infected individuals. Therefore, identifying individuals at this stage is crucial to enable early intervention. Therefore, we assessed impaired fasting glucose (IFG) and associated factors among perinatally HIV-infected population in Dar es salaam Tanzania.MethodsA cross-sectional study was conducted among 152 adolescents and youth attending HIV clinic at Muhimbili National Hospital and Infectious Disease Centre from July to August 2020. Fasting blood glucose (>8 hours) was measured using one-touch selects LifeScan, CA, USA. We also examined C-Reactive Protein and interleukin-6 inflammatory biomarkers in relation to impaired fasting glucose (IFG). Associations between categorical variables were explored using Chi-square, and poison regression with robust variance was used to calculate the prevalence ratios.ResultsOf the 152 participants, the majority were male (n=83[54.6%]), and the median age was 15(14-18) years. Overweight or obesity was prevalent in 16.4%, while more than one in ten (13.2%) had high blood pressure (≥149/90mmHg). All participants were on antiretroviral therapy (ART); 46% had used medication for over ten years, and about one in three had poor medication adherence. Among the recruited participants, 29% had impaired fasting glucose. The odds of IFG were two times higher in males compared to females (PR, 2.07, 95% CI 1.19 -3.59 p=0.001). Moreover, we found with every increase of Interleukin 6 biomarker there was a 1.01 probability increase of impaired fasting glucose (PR, 1.01, 95% CI 1.00 - 1.02 p=0.003).ConclusionAbout one in three perinatally HIV-infected youths had impaired fasting glucose in Dar es Salaam, Tanzania, with males bearing the biggest brunt. Moreover, with every increase of 1.101 of the probability of having IFG increased. This calls for urgent measures to interrupt the progression to diabetes disease and prevent the dual burden of disease for this uniquely challenged population.

Project description:To investigate the mechanism and functional significance of infection of CD8+ lymphocytes by human immunodeficiency virus type 1 (HIV-1) in vivo, we determined frequencies of infection, proviral conformation, and genetic relationships between HIV-1 variants infecting naive (CD45RA+) and memory (CD45RO+) peripheral blood CD4+ and CD8+ lymphocytes. Infection of CD3+ CD8+ CD45RA+ cells was detected in 9 of 16 study subjects at frequencies ranging from 30 to 1,400 proviral copies/10(6) cells, more frequently than CD3+ CD8+ lymphocytes expressing the RO isoform of CD45 (n = 2, 70 and 260 copies /10(6) cells). In agreement with previous studies, there was no evidence for a similar preferential infection of CD4+ naive lymphocytes. Proviral sequences in both CD4+ and CD8+ lymphocyte subsets were complete, as assessed by quantitation using primers from the long terminal repeat region spanning the tRNA primer binding site. In six of the seven study subjects investigated, variants infecting CD8+ lymphocytes were partially or completely genetically distinct in the V3 region from those recovered from CD4+ lymphocytes and showed a greater degree of compartmentalization than observed between naive and memory subsets of CD4+ lymphocytes. In two study subjects, arginine substitutions at position 306, associated with use of the chemokine coreceptor CXCR4, were preferentially found in CD4 lymphocytes. These population differences may have originated through different times of infection rather than necessarily indicating a difference in their biological properties. The preferential distribution of HIV-1 in naive CD8+ lymphocytes indeed suggests that infection occurred early in T-lymphocyte ontogeny, such as during maturation in the thymus. Destruction of cells destined to become CD8+ lymphocytes may be a major factor in the decline in CD8+ lymphocyte frequencies and function on disease progression and may contribute directly to the observed immunodeficiency in AIDS.

Dataset Information

Gag-Specific CD8 T-Cell Proliferation Is Associated With Higher Peripheral Blood Levels of Transforming Growth Factor-β and Gut-Homing T Cells in Youths Perinatally Infected With Human Immunodeficiency Virus-1: The ANRS-EP38-IMMIP Study.

Background

Methods

Results

Conclusions

Publications

Gag-Specific CD8 T-Cell Proliferation Is Associated With Higher Peripheral Blood Levels of Transforming Growth Factor-β and Gut-Homing T Cells in Youths Perinatally Infected With Human Immunodeficiency Virus-1: The ANRS-EP38-IMMIP Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets