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Comprehensive screening reveals strong and broadly directed human immunodeficiency virus type 1-specific CD8
M E Feeney1, K A Roosevelt, Y Tang
1Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical Schoo, Boston, Massachusetts, USA.
Insights
Pediatric HIV-1 infection survivors mount robust CD8 T-cell responses comparable to adults. These immune responses, though weaker with suppressed viremia, show potential for broadening with immunotherapeutic interventions.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Antiviral therapy has increased lifespan for children with perinatally acquired HIV-1.
- Immune responses to HIV-1 in children are not well understood.
- Previous studies showed weak cellular immunity in early infancy.
Purpose of the Study:
- To comprehensively characterize HIV-1-specific CD8 T-cell responses in perinatally infected children.
- To compare these responses to those in HIV-1-infected adults.
- To assess the potential for immunotherapeutic interventions in this population.
Main Methods:
- Studied 18 perinatally HIV-1-infected children (ages 6-17).
- Utilized defined HIV-1 epitopes and overlapping peptides for comprehensive response assessment.
- Analyzed CD8 T-cell responses in peripheral blood mononuclear cells.
Main Results:
- All subjects exhibited multispecific CD8 T-cell responses targeting multiple HIV-1 proteins, comparable to adults.
- Responses were broadly directed, with a median of 0.25-0.3% of PBMCs.
- Breadth and magnitude were lower in children with suppressed viremia on antiretroviral therapy.
Conclusions:
- Perinatally infected children mount robust HIV-1-specific CD8 T-cell responses, stronger than previously thought.
- These responses are comparable in magnitude and breadth to adult responses.
- Children with HIV-1 are potential candidates for immunotherapeutic interventions due to responsive immune systems.
Abstract:
Advances in antiviral therapy have dramatically shifted the demographics of pediatric human immunodeficiency virus type 1 (HIV-1) infection in the developed world, and a growing proportion of perinatally HIV-1-infected children are now entering their second or even third decade of life. Although cellular immune responses to HIV are known to be weak in early infancy, the magnitude, breadth, and specificity of responses later in childhood have not been characterized in detail. We performed a comprehensive characterization of HIV-1-specific CD8 responses in 18 perinatally infected children (age range, 6 to 17 years), most of whom were on antiviral therapy, using both previously defined HIV-1 epitopes and overlapping peptides spanning all HIV-1 proteins. Multispecific responses were detected in all subjects and accounted for a median of 0.25 to 0.3% of all peripheral blood mononuclear cells that was similar to the magnitude seen in HIV-infected adults. CD8 responses were broadly directed at an average of 11 epitopes (range, 2 to 27 epitopes) and targeted nearly all HIV-1 proteins, with the highest proportion in Gag. Responses were readily detected even in those children with suppressed viremia on highly active antiretroviral therapy, although the breadth (P = 0.037) and the magnitude (P = 0.021) were significantly lower in these subjects. Each child recognized only a small minority of the HIV-1 optimal epitopes defined for his or her class I HLA alleles. Together, these data indicate that perinatally infected children who survive infancy mount a robust HIV-1-specific CD8 response that is much stronger than previously thought and is comparable in magnitude and breadth to that of adults. Moreover, this response has the potential to be broadened to target more epitopes, making these children attractive candidates for immunotherapeutic interventions.