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Lymphoproliferative responses to mitogen and antigen in HIV-infected children
J P Johnson1, R Hebel, R Shinaberry
1Department of Pediatrics, University of Maryland, Baltimore.
Insights
Children with human immunodeficiency virus (HIV) infection show early loss of antigen response, preceding immune cell decline. Infants are especially vulnerable to HIV immunopathogenesis.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Virology
Background:
- Children with human immunodeficiency virus (HIV) infection exhibit distinct immunological profiles compared to adults.
- Infancy represents a period of relative immunodeficiency, potentially increasing susceptibility to HIV infection's effects.
Purpose of the Study:
- To investigate lymphoproliferative responses in children with HIV infection.
- To compare these responses with those of healthy control children.
- To analyze age- and disease-stage-specific immune changes in pediatric HIV.
Main Methods:
- Categorized children by age (6-18 months, >18 months) and CDC classification (P1, P2A, P2D).
- Measured absolute CD4 and CD8 cell counts.
- Assessed lymphoproliferative responses to phytohemagglutinin A (PHA) and tetanus toxoid.
Main Results:
- Absolute CD4 and CD8 counts were higher in younger children.
- HIV-infected children in P1 and P2A classes showed increased CD8+ cells; only AIDS (P2D) cases had decreased CD4+ cells.
- Significant decrease in PHA response observed in older AIDS (P2D) and younger symptomatic (P2A, P2D) children.
- All HIV-infected children showed a significant decrease in response to tetanus toxoid.
- Loss of antigen responsiveness preceded loss of mitogenic responsiveness (PHA).
- Age-related increase in lymphoproliferative responses noted in both HIV-infected and control children.
Conclusions:
- Children are highly susceptible to the immunologic effects of HIV infection.
- Loss of lymphoproliferative responses to antigen occurs early in pediatric HIV infection, before CD4+ cell loss or reduced PHA response.
- Infants' relative immunodeficiency contributes to their increased susceptibility to HIV immunopathogenesis.
Abstract:
We endeavored to study lymphoproliferative responses in children with human immunodeficiency virus (HIV) infection and to compare them with normal control children. Children were grouped according to age; 6-18 months and greater than 18 months, and according to CDC classification: asymptomatic (P1), mildly symptomatic (P2A), and advanced symptoms (P2D). Absolute CD4 and CD8 numbers were compared and found to be higher in the younger age groups. The children in P1 and P2A classes demonstrated an increase in CD8+ cells; only the children with AIDS showed a significant decrease in CD4+ cells. Lymphoproliferative responses to phytohemagglutinin A (PHA) were compared to tetanus toxoid. Only the children with acquired immunodeficiency syndrome (AIDS) (P2D) in the older group and only the symptomatic children (P2A and P2D) in the younger group showed a significant decrease in proliferative responses to PHA. All classes of infected children demonstrated a significant decrease in response to tetanus toxoid. We have been able to demonstrate a loss of antigen responsiveness which precedes the loss of mitogenic responsiveness. Furthermore, we have been able to demonstrate an age related increase in lymphoproliferative responses to both PHA and tetanus in HIV-infected and control children. Therefore, we conclude that children are particularly susceptible to the immunologic effects of HIV infection. Loss of lymphoproliferative responses to antigen occurs early in infected children and precedes the loss of CD4+ helper cells and of PHA responsiveness. This increased susceptibility to the immunopathogenesis of HIV infection is due, at least in part, to the relative immunodeficiency of infancy.