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1.
Immun Ageing ; 16: 14, 2019.
Article in English | MEDLINE | ID: mdl-31312227

ABSTRACT

BACKGROUND: Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness. METHODS: Subjects (> 60 years old) who were vaccinated against influenza virus were included, and the vaccine response was measured by a haemagglutination inhibition (HAI) test. At baseline, peripheral CD4 and CD8 T-cells were phenotypically characterized. Thymic function and the levels of different inflammation-related biomarkers, including Lipopolysaccharide Binding Protein (LBP) and anti-cytomegalovirus (CMV) IgG antibodies, were also measured. RESULTS: Influenza vaccine non-responders showed a tendency of higher frequency of regulatory T-cells (Tregs) before vaccination than responders (1.49 [1.08-1.85] vs. 1.12 [0.94-1.63], respectively, p = 0.061), as well as higher expression of the proliferation marker Ki67 in Tregs and different CD4 and CD8 T-cell maturational subsets. The levels of inflammation-related biomarkers correlated with the frequencies of different proliferating T-cell subsets and with thymic function (e.g., thymic function with D-dimers, r = - 0.442, p = 0.001). CONCLUSIONS: Age-related homeostatic dysregulation involving the proliferation of CD4 and CD8 T-cell subsets, including Tregs, was related to a limited responsiveness to influenza vaccination and a higher inflammatory status in a cohort of elderly people.

2.
Article in English | MEDLINE | ID: mdl-28559274

ABSTRACT

We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , CD4-CD8 Ratio , CD8-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV Infections/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Anti-HIV Agents/therapeutic use , Biomarkers/metabolism , Cell Survival/drug effects , Didanosine/therapeutic use , Female , Humans , Male , Middle Aged , Receptors, CXCR4/immunology , Stavudine/therapeutic use , Viral Load , Zalcitabine/therapeutic use , Zidovudine/therapeutic use
3.
Clin Infect Dis ; 64(2): 152-158, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-27986677

ABSTRACT

BACKGROUND: The persistence of an inverted CD4/CD8 ratio has been extensively associated with the increased morbimortality of chronic human immunodeficiency virus (HIV)-infected subjects. Thymic function is crucial for the maintenance of T cell homeostasis. We explored the impact of thymic function on the CD4/CD8 ratio of HIV-infected subjects. METHODS: In a cohort of 53 antiretroviral-naive HIV-infected subjects, the measure of thymic volume, as a representative marker for thymic function, was available at baseline and at 12, 24, and 48 weeks post antiretroviral treatment. RESULTS: Baseline thymic volume was associated with the CD4/CD8 ratio ( Ρ: = 0.413, P = .002), being this association highly dependent on the CD4 T cell levels. In subjects who achieved undetectable viral load after treatment (n = 33), a higher baseline thymic volume was associated with a higher increase in CD4 T cell counts and a decreasing trend in CD8 T cell counts during follow-up. Moreover, the baseline thymic volume was independently associated with the normalization of the CD4/CD8 ratio after 96 weeks of treatment (odds ratio, 95% confidence interval: 1.95 (1.07-3.55); P = .03). CONCLUSIONS: Our data indicate the relevance of the remaining thymic function before the start of treatment to the CD4/CD8 ratio of HIV- infected subjects and, hence, potentially, in their clinical progression.


Subject(s)
CD4-CD8 Ratio , HIV Infections/immunology , HIV Infections/virology , HIV-1/immunology , Thymus Gland/anatomy & histology , Thymus Gland/physiology , Adult , Antiretroviral Therapy, Highly Active , Biomarkers , CD4 Lymphocyte Count , Female , HIV Infections/blood , HIV Infections/drug therapy , Humans , Immunophenotyping , Male , Organ Size , Phenotype , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Thymus Gland/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Viral Load
4.
Clin Microbiol Infect ; 22(5): 461.e1-5, 2016 May.
Article in English | MEDLINE | ID: mdl-26806257

ABSTRACT

Regulatory T (Treg) cells comprise different functional subsets with different CCR5 expression. Treg homeostasis is disrupted by HIV but the effect of treatment has barely been explored. In a longitudinal design, we compared the effect of a maraviroc-containing (n = 9) or sparing (n = 12) therapy in antiretroviral-naive HIV-positive participants on peripheral FoxP3(low) CD45RA(+) (nTreg), FoxP3(high) CD45RA(-) (eTreg) and FoxP3(low) CD45RA(-) (non-Treg) cells. Maraviroc significantly reduced all subsets in the short-term and, except for nTreg cells, also normalized them in the long-term. The correlation between eTreg cells and CD4 counts, lost before treatment, was only restored by maraviroc. The differential effect of maraviroc on Treg subsets contributes to understanding its immunomodulatory effects.


Subject(s)
CCR5 Receptor Antagonists/therapeutic use , Cyclohexanes/therapeutic use , HIV Infections/drug therapy , HIV Infections/immunology , Homeostasis , T-Lymphocytes, Regulatory/immunology , Triazoles/therapeutic use , CD4 Lymphocyte Count , Forkhead Transcription Factors/analysis , Humans , Immunophenotyping , Leukocyte Common Antigens/analysis , Longitudinal Studies , Maraviroc , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/chemistry
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