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Updated: May 18, 2026
New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals
Published on: May 30, 2013
Age-related expansion of Tim-3 expressing T cells in vertically HIV-1 infected children
Ravi Tandon1, Maria T M Giret, Devi Sengupta
1Hawaii Center for AIDS, Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. rtandon@hawaii.edu
Insights
As children with perinatal HIV-1 infection age, T cell exhaustion worsens. The study found increased Tim-3 expression, linked to viral load and age, suggesting it drives T cell dysfunction and offers a therapeutic target.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Perinatally HIV-1-infected individuals face long-term immune challenges.
- Immune exhaustion, characterized by T cell dysfunction, is known in adults but poorly understood in vertical HIV-1 infection.
- Antiretroviral therapy (ART) is standard, but long-term immune consequences persist.
Purpose of the Study:
- To investigate T cell dysfunction and exhaustion phenotypes in adolescents and young adults with perinatally acquired HIV-1 infection.
- To compare immune profiles between younger children and older adolescents with vertical HIV-1 infection.
- To identify specific immune markers associated with age-related T cell dysfunction in this population.
Main Methods:
- Analysis of T cell senescence (CD28(-)CD57(+)) and exhaustion markers (PD-1, Tim-3) on CD8(+) and CD4(+) T cells.
- Comparison between two ART-treated perinatally HIV-1-infected groups with different median ages (11.2 yr and 18.5 yr).
- Correlation analysis between immune markers, age, duration of infection, and HIV-1 viral load.
Main Results:
- No significant difference in senescent T cells (CD28(-)CD57(+)) between age groups.
- Significantly higher frequencies of Tim-3(+) exhausted T cells (CD8(+) and CD4(+)) in older adolescents compared to younger children.
- PD-1(+) T cells were associated with immune activation in children, while Tim-3(+) T cells correlated with viral load in adolescents.
Conclusions:
- Tim-3 upregulation is associated with both HIV-1 viral replication and increasing age in perinatally infected individuals.
- The Tim-3 immune exhaustion phenotype, not PD-1 or senescence, appears crucial for age-related T cell dysfunction.
- Targeting Tim-3 presents a potential therapeutic strategy to improve immune control and mitigate T cell exhaustion in vertically HIV-1-infected individuals.
Abstract:
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.
