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Published on: January 5, 2016
Changes in cellular immune activation and memory T-cell subsets in HIV-infected Zambian children receiving HAART
Kaitlin Rainwater-Lovett1, Hope Nkamba, Mwangelwa Mubiana-Mbewe
1*Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; †Virology Laboratory, University Teaching Hospital, Lusaka, Zambia; ‡Center for Infectious Disease Research-Zambia, Lusaka, Zambia; §Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL; and ‖Department of W. Harry Feinstone Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (Dr Kaitlin Rainwater-Lovett is now with Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD; Carolyn B. Moore is now with Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC).
Insights
Highly active antiretroviral therapy (HAART) in Zambian children with HIV reduced immune activation and effector memory CD4+ T cells. However, effector memory T cells remained elevated, suggesting ongoing immune system changes.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- HIV/AIDS Research
Background:
- Sub-Saharan African children face high pathogen exposure, potentially increasing immune activation and memory T cells.
- Understanding T-cell subset dynamics during highly active antiretroviral therapy (HAART) is crucial for immune restoration in young children with HIV in this region.
Purpose of the Study:
- To characterize changes in CD4+ and CD8+ T-cell subsets in HIV-infected Zambian children receiving HAART.
- To assess the impact of HAART on immune activation and T-cell memory populations.
Main Methods:
- Flow cytometry was used to measure T-cell subsets in 157 HIV-infected children before and during HAART (up to 30 months).
- A control group of 34 children was included for comparison.
- Longitudinal follow-up data were collected at 3-month intervals.
Main Results:
- Before HAART, HIV-infected children exhibited higher immune activation and effector memory (EM) T cells, with lower naive T cells and IL-7Rα-expressing CD8+ T cells compared to controls.
- HAART led to a decline in immune activation and EM CD4+ T cells within 6 months.
- Persistently elevated EM CD4+ T cells and effector CD8+ T cells were observed up to 30 months, while IL-7Rα-expressing CD8+ T cells increased, indicating potential memory capacity expansion.
Conclusions:
- HAART effectively reduces immune activation and EM CD4+ T cells, while promoting naive T-cell and IL-7Rα-expressing CD8+ T-cell reconstitution.
- Sustained high levels of EM CD4+ T cells suggest persistent alterations in T-cell subset composition in HIV-infected children despite HAART.
Background:
Increased exposure to a broad array of pathogens in children residing in sub-Saharan Africa may lead to heightened immune activation and increased proportions of memory T cells. Changes in the size of these cellular subsets have implications for restoration of normal immune function after treatment with highly active antiretroviral therapy (HAART) and are not well characterized in young sub-Saharan African children.
Methods:
CD4⁺ and CD8⁺ T-cell subsets were measured by flow cytometry in 157 HIV-infected Zambian children before and at 3-month intervals during HAART for up to 30 months and in 34 control children at a single study visit.
Results:
Before HAART, HIV-infected children had higher levels of activated and effector memory (EM) CD4⁺ and CD8⁺ T cells, and lower levels of naive T cells and CD8⁺ T cells expressing IL-7Rα, compared with control children. The median duration of follow-up was 14.9 months (interquartile range, 6.4-23.2) among 120 HIV-infected children with at least 1 study follow-up visit. Levels of immune activation and EM CD4⁺ T cells declined within 6 months of HAART, but the percentages of EM CD4 T cells and effector CD8⁺ T cells remained elevated through 30 months of HAART. IL-7Rα-expressing CD8⁺ T cells increased with HAART, suggesting expansion of memory capacity.
Conclusions:
HAART significantly reduced levels of immune activation and EM CD4⁺ T cells, and promoted reconstitution of naive T cells and IL-7Rα-expressing CD8⁺ T cells. However, persistently high levels of EM CD4⁺ T cells in HIV-infected children may reflect chronic perturbations in T-cell subset composition.
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