Further Evidence That the Expression of CD38 and HLA-DR<sup>+</sup> in CD8<sup>+</sup> Lymphocytes Does Not Correlate to Disease Progression in HIV-1 Vertically Infected Children

Romeiro, Juliana Ribeiro; Pinto, Jorge; Silva, Maria Luíza; Elói-Santos, Silvana Maria

doi:10.1177/1545109711421642

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…We and others have shown that HIV-1 viral load directly associates with T cell activation (HLA-DR + CD38 + or CD38 + ) in adults [53], [54], but this does not appear to occur in pediatric vertical infection which has also been confirmed by others [55]. Tim-3 + CD8 + T cells are not associated with T cell activation [30].…”

Section: Discussionsupporting

confidence: 66%

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

et al. 2012

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As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an “immune exhaustion”, with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28−CD57+CD8+ T cells between the groups. However, the frequency of Tim-3+CD8+ and Tim-3+CD4+ exhausted T cells, but not PD-1+ T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1+CD8+ T cells were directly associated with T cell immune activation in children. The frequency of Tim-3+CD8+ T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.

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Section: Discussionsupporting

confidence: 66%

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

et al. 2012

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“…Romeiro et al . [ 106 ] found that a higher percentage of activated CD8 + T cells was present in all HIV-infected children regardless of disease progression, and that CD8 + T cell activation was not associated with the viral load or the percentage of CD4 + T cells. Therefore, it was concluded that the expression of CD38 in CD8 + lymphocytes from HIV vertically infected children was not associated with disease progression, and these immunological parameters could not be applied to the prognostic assessment.…”

Section: The Cd38 Moleculementioning

confidence: 99%

“…It has been reported that CD38 is expressed early in hematopoietic cells, with downregulation during the cell maturation process and re-expression upon cell activation. This cyclic nature of CD38 expression during lymphopoietic ontogeny may explain the expression of CD38 in HIV-infected children [ 106 ].…”

Section: The Cd38 Moleculementioning

confidence: 99%

The role of CD38 in HIV infection

Wang

Yang³

et al. 2021

AIDS Res Ther

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The widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression through different mechanisms. Therefore, investigating the role of CD38 in HIV infection and the potential signaling pathways that are involved may provide a new perspective on potential treatments for HIV infection. In the present review, the current understanding of the roles CD38 plays in HIV infection are summarized. In addition, the specific role of CD38 in the process of HIV infection of human CD4+ T lymphocytes is also discussed.

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Longitudinal Changes in Subclinical Vascular Disease in Ugandan Youth With Human Immunodeficiency Virus

Dirajlal-Fargo

Zhao

Labbato

et al. 2022

Clinical Infectious Diseases

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Introduction The risk of cardiovascular disease (CVD) and prospective investigations in youth living with perinatally acquired HIV (PHIV) in sub-Saharan Africa are lacking. Methods A prospective observational cohort study was performed in 101 PHIV and 97 HIV-, 10-18 years of age, from 2017-2021 at the JCRC in Uganda. PHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. Common carotid artery intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated at baseline and 96 weeks. Groups were compared using unpaired t test and potential predictors of IMT and PWV were assessed using quantile regression. Results Of the 198 participants recruited at baseline, 168 (89 PHIV, 79 HIV-) had measurements at 96 weeks. Median (Q1, Q3) age was 13 years (11,15); 52% were females; 85% had viral load < 50 copies/mL and remained undetectable at week 96. Baseline mean common carotid IMT was slightly higher in PHIVs compared to controls (p < 0.01), and PWV did not differ between groups(p = 0.08). At week 96, IMT decreased and PWV increased in PHIV (p≤0.03); IMT increased in HIV- (p = 0.03) with no change in PWV (p = 0.92). In longitudinal analyses in PHIV, longer ART duration was associated with lower PWV (β=0.008, 95% CI -0.008, 0.003), and abacavir use with greater IMT (β=0.043, 95% CI 0.012, 0.074). Conclusions In healthy Ugandan PHIV, with viral suppression on ART, common carotid IMT did not progress over 2 years. Prolonged and early ART may prevent progression of subclinical vascular disease, while prolonged use of abacavir may increase it.

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Further Evidence That the Expression of CD38 and HLA-DR⁺ in CD8⁺ Lymphocytes Does Not Correlate to Disease Progression in HIV-1 Vertically Infected Children

Abstract: HIV-1-infected children presented an increased percentage of activated CD8(+) T cells and an unaltered percentage of Treg cells, regardless of their clinical evolution. Thus, these immunological parameters should not be used for prognostic evaluation.

Cited by 7 publications

References 21 publications

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

The role of CD38 in HIV infection

Longitudinal Changes in Subclinical Vascular Disease in Ugandan Youth With Human Immunodeficiency Virus

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Further Evidence That the Expression of CD38 and HLA-DR+ in CD8+ Lymphocytes Does Not Correlate to Disease Progression in HIV-1 Vertically Infected Children

Abstract: HIV-1-infected children presented an increased percentage of activated CD8(+) T cells and an unaltered percentage of Treg cells, regardless of their clinical evolution. Thus, these immunological parameters should not be used for prognostic evaluation.

Cited by 7 publications

References 21 publications

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

The role of CD38 in HIV infection

Longitudinal Changes in Subclinical Vascular Disease in Ugandan Youth With Human Immunodeficiency Virus

Contact Info

Product

Resources

About

Further Evidence That the Expression of CD38 and HLA-DR⁺ in CD8⁺ Lymphocytes Does Not Correlate to Disease Progression in HIV-1 Vertically Infected Children