T cell activation in pediatric AIDS pathogenesis: three-color immunophenotyping

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 > or = 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 > or = 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 > or = 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 > or = 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 > or = 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.(ABSTRACT TRUNCATED AT 400 WORDS)