T Cell Activation in Pediatric AIDS Pathogenesis: Three-Color Immunophenotyping

Abstract

Immune activation is an important component of HIV disease in adults that may reflect a protective host response and/or be a component of immunopathogenesis. The goals of this study were to gain understanding of T cell activation in pediatric HIV disease, to assess the usefulness of T cell activation markers as surrogates for disease progression and/or early identification of infection in infants at risk, and to determine any advantages of three- compared to two-color flow cytometric immunophenotyping for the above assessments. We examined the expression of cell-surface activation antigens on the CD4 and CD8 T cells of 26 HIV-infected and 40 HIV-seronegative age-matched control children. Compared with controls, HIV-infected children showed a slight but not significant decrease in the proportion of CD4 cells that coexpressed CD45RA and L-selectin (mean of 83 vs 75% for <2 years of age, 76 vs 62% for 2-3 years, 64 vs 56% for ⩾4 years). CD4 cells coexpressing CD38 and HLA-DR were significantly increased in HIV + children (mean of 2 vs 6% for <2 years of age, 3 vs 11% for 2-3 years, 2 vs 8% for ⩾4 years). There was a striking and significant increase in the proportion of CD8 cells coexpressing CD38 and HLA-DR (mean of 5 vs. 25% for <2 years, 10 vs 41% for 2-3 years, 6 vs 31% for ⩾4 years); this double positive population of CD8 cells included cells that were approximately 1 log brighter for the expression of CD38 than for that of CD38 single-positive cells. There was a significant reduction in CD45RA + CD8 cells (means of 92 vs 71% for <2 years of age, 88 vs 50% for 2-3 years, 80 vs 57% for ⩾4 years) and an increase in CD57 + CD8 cells (mean of 4 vs 8% for <2 years of age, 8 vs 22% for 2-3 years, 19 vs 31% for ⩾ 4 years) in HIV + children. The inclusion of CD3 as an anchor marker for CD8 cell subsets to limit the analysis to CD3 + CD8 cells did not substantially alter the data nor enhance the differences between infected and control children compared with the analysis of all CD8 cells. The phenotypic alterations were not clear diagnostic markers of infection in young at-risk children, but may be useful in association with other laboratory or clinical information in the identification of infected P-0 children. T cell activation antigens also may serve as markers of disease progression in HIV + children.