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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
[Different immune profiles according to the immunological and clinical progression in vertically HIV-infected
Salvador Resino1, M Luisa Abad, José M Bellón
1Servicio de Inmunología. Hospital General Universitario Gregorio Marañón. Madrid. Spain.
Insights
HIV-infected children on antiretroviral treatment (ART) show distinct immunologic profiles based on disease stage. Despite ART, differences in T-cell subsets and cytokine production persist, highlighting the impact of HIV progression on immune status.
Area of Science:
- Immunology
- Virology
- Pediatrics
Context:
- Human Immunodeficiency Virus (HIV) infection in children requires ongoing management with antiretroviral treatment (ART).
- Understanding the long-term immunologic consequences of HIV infection, even with treatment, is crucial for patient care.
- Assessing immune system recovery and persistent alterations in HIV-infected children is an active area of research.
Purpose:
- To evaluate and compare the immunologic profile differences in vertically HIV-infected children undergoing ART, categorized by disease stage (A1, B2, C3).
- To investigate variations in T-cell subsets, cell proliferation, and cytokine production among different HIV disease categories and healthy controls.
Summary:
- HIV-infected children on ART exhibited varied T-cell subset compositions (e.g., CD8+ CD45RA+ CD62L+, CD8+ CD45RO+) and cytokine production (e.g., TNF-alpha) compared to controls.
- Cell proliferation responses differed significantly between disease stages, with higher indexes in the less advanced A1 group.
- Advanced HIV stages (B2, C3) showed distinct patterns of T-cell activation and exhaustion markers (e.g., CD38, HLA-DR) compared to the A1 group and controls.
Impact:
- The findings underscore that ART does not fully normalize the immune system in all HIV-infected children, with persistent immunologic differences linked to disease stage.
- This research provides valuable insights for tailoring therapeutic strategies and monitoring immune reconstitution in pediatric HIV management.
- Understanding these immunologic disparities can inform prognosis and the development of novel immunomodulatory interventions for HIV-infected children.
Background:
Our goal was to evaluate immunologic profile differences of HIV-infected children on antiretroviral treatment (ART). PATIENTS AND METHODDS: We studied 23 HIV-vertically infected children: a) N-A1 group: 10 HIV-infected children in A1 category; b) N-B2 group: 6 HIV-infected children in B2 category, and c) N-C3 group: 7 HIV-infected children in C3 category. We also studied 13 healthy age-matched HIV-negative children as controls. Cell proliferation was evaluated by incorporation of [3H]-Thymidine. The cytokine production in culture was quantified using commercially available specific ELISA assays. T-cell subsets were determined by flow cytometry.
Results:
Stimulation indexes of PHA, PWM, and anti-CD3+ anti-CD28 in N-A1 group were higher than in N-C3 group. In unstimulated PBMC, TNF-alpha production of HIV-infected children was higher than the control group (p < 0.05). However, in stimulated PBMC, TNF-alpha production in N-B2 and N-C3 groups was lower than the control group (p < 0.05). In HIV-infected children, CD8+ CD45RA+ CD62L+ T-cells were significantly lower (p < 0.01) and CD8+ CD45RO+ T-cells were higher (p < 0.05) than the control group. Moreover, in NA-1 group, CD4+ CD45RA+ CD62L+ T-cells were higher, and CD4+ CD45RO+ and CD8+ CD45RO+ T-cells were lower, than in N-B2 and N-C3 groups (p < 0.05). On the other hand, CD45RO+, CD45RO+ CD38+, HLA-DR+, CD38+ HLA-DR+ and CD38+ CD4+ and CD8+ T-cells were higher in N-C3 group than the N-A1 and control groups, except for CD4+ CD38+ T-cells. Activated CD8+ T-cells in N-A1 group were higher than in control group (p < 0.01).
Conclusion:
Our data demonstrate that in spite of ART, there still remain important differences in the immunologic status of HIV-infected children depending on the HIV-infection stage.
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