Related Experiment Videos
Preserved immune system in long-term asymptomatic vertically HIV-1 infected children
S Resino1, R Correa, J M Bellón
1Laboratory of Immno-Molecular Biology, General University Hospital 'Gregorio Marañón', Madrid, Spain.
Insights
Long-term asymptomatic HIV-1 infected children maintain a preserved immune system, similar to controls, despite prolonged infection. New markers like TRECs and IL-7 can monitor disease progression in HIV.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) infection can lead to varied clinical outcomes in children.
- Long-term asymptomatic (LTA) status in HIV-1 infected children suggests a preserved immune system, but requires detailed characterization.
- Understanding immune status in LTA children is crucial for monitoring disease and identifying potential biomarkers.
Purpose of the Study:
- To investigate the immune system status of long-term asymptomatic (LTA) HIV-1 infected children.
- To compare immune parameters between LTA children, rapid progressor (RP) HIV-1 infected children, and healthy controls.
- To identify potential biomarkers for monitoring HIV disease progression.
Main Methods:
- Cross-sectional study of HIV-1 infected children (>7 years) categorized as LTA or RP, compared to uninfected controls.
- Flow cytometry used to characterize CD4+ T-cell subsets (memory, naive, activation markers).
- Assessed T-cell proliferative responses, cytokine production (TNF-alpha, IFN-gamma), serum IL-7 levels, and thymic T-cell production (TRECs).
Main Results:
- LTA children exhibited preserved T-cell proliferative responses and cytokine production (TNF-alpha, IFN-gamma) compared to RP children, similar to controls.
- LTA children showed distinct CD4+ T-cell subset profiles: lower memory cells, higher naive cells, and increased activation markers (HLA-DR, CD38) compared to controls.
- Near-normal TRECs and IL-7 levels were observed in LTA children, contrasting with lower levels in RP children, with an inverse correlation between TRECs and IL-7.
Conclusions:
- Asymptomatic HIV-1 infected children demonstrate a well-preserved immune system, comparable to uninfected children, even after over 7 years of infection.
- CD4+ T-cell subset analysis reveals specific patterns in LTA children, indicating immune adaptation.
- TRECs and IL-7 levels emerge as potential novel biomarkers for monitoring HIV disease status in children.
Abstract:
The objective of this study was to study immune system status in long-term asymptomatic (LTA) HIV-1-infected children. A cross-sectional study was used, involving HIV-1-infected children over 7 years of age who were rated into two groups according to their clinical and immunological classification: (a) LTA: 7 asymptomatic HIV-1-infected children in A1; (b) Rapid progressor (RP): 14 age-matched C3 HIV-1-infected children. The control group consisted of 17 age-matched uninfected children. The characterization of CD4+ T-cell subsets was determined by three-colour flow cytometry. The proliferative response and cytokine production by activated peripheral blood T-cells were also measured. IL-7 levels were measured in serum. Thymic production of T-cells was quantified by TCR rearrangement excision circles (TRECs). The LTA children showed similar proliferative responses to PHA, PWM and anti-CD3+ anti-CD28, but lower responses to tetanus toxoid and streptokinase, in comparison with the controls but always higher responses in comparison with the RP group. The production of TNF-alpha and IFN-gamma was similar in the LTA and control groups, and both were higher than the levels in the RP group. The LTA group showed a lower percentage of memory CD4+ T-cells (CD4+ CD45RO+, CD4+ CD45RA-CD62L+) than the control and RP groups. The LTA group also showed lower percentages of CD4+ CD7- cells than the controls. As for naïve CD4+ T-cells (CD4+ CD45RA+ CD62L+), CD4+ CD45RA+ and CD4+ CD62L+ cells, the LTA group showed higher values than the control and RP groups. The LTA group showed higher percentages of CD4+ HLA-DR+ CD38+ than the controls, but lower values than the RP group. In contrast, the LTA group had percentages of CD4+ HLA-DR-CD38+ T-cells higher than both the control and RP groups, whereas CD4+ CD38+ levels were only higher in the LTA group in comparison with the controls. CD4+ HLA-DR+ CD38- and CD4+ HLA-DR+ cell numbers were lower in the LTA group in comparison with the RP group. We found almost normal values of TRECs and IL-7 in the LTA group, but lower values in the RP group. Moreover, we found an inverse relation between TREC levels and IL-7 in plasma from HIV-infected children. Asymptomatic HIV-1 infected children have a well preserved immune system similar to that of control uninfected children in spite of HIV-infection for more than 7 years. Moreover, our results identified new markers of HIV disease, such as TRECs and IL-7, that could be used to monitor disease.