Different Meaning of CD38 Molecule Expression on CD4+ and CD8+ Cells of Children Perinatally Infected with Human Immunodeficiency Virus Type 1 Infection Surviving Longer than Five Years

Abstract

We investigated the relationship between CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell proportions (HLA-DR = major histocompatibility complex class II) (determined by two-color immunofluorescence) and the clinical condition, IL-2 and IL-6 production, viral RNA copy numbers, and the eventual immunologic-virologic course in 25 children perinatally infected with HIV-1 surviving longer than 5 y [median age, 92 (range, 63-136) mo]. Twelve healthy age-matched children were studied as control subjects. HIV-1+ children had lower percentages and absolute numbers of CD4+CD38+, whereas the percentages of CD4+HLA-DR+ and the percentages and absolute numbers of CD8+CD38+ and CD8+HLA-DR+ cells were higher than that of control subjects. The absolute numbers of CD4+ and the percentages of CD4+CD38+, CD8+CD38+, and CD8+HLA-DR+ cells directly correlated, whereas the percentages of CD4+CD38+ and CD4+HLA-DR+ cells, the percentages of CD4+CD38+ and CD8+CD38+ cells, the CD8+ cell absolute numbers, and the percentages of CD8+CD38+ cells did not. Severe manifestations and immunologic deterioration occurred in children with low CD4+CD38+ cell percentages, whereas virologic worsening was associated with low CD8+CD38+ and CD8+HLA-DR+ cell percentages. IL-2 production directly correlated with percentages and absolute numbers of CD4+CD38+ and CD8+CD38+ cells. RNA copy numbers inversely correlated with CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell percentages. This suggests that CD38 molecule expression on both CD4+ and CD8+ cell subsets is a favorable marker in HIV-1+ children. Perhaps CD8+CD38+ subsets are activated cells, whereas CD4+CD38+ subsets are immature cells, possibly the host's attempt at CD4+ cell renewal.

CD38 Expression on CD8+ T Cells as a Prognostic Marker in Vertically HIV-Infected Pediatric Patients

“…The %CD8 ϩ CD38 ϩ and CD8 ϩ (CD38 ϩ ) measurements are highly correlated, but the latter is preferable because of the heterogeneous expression of CD38 on the cell surface (2,6,12,13). This study confirmed that CD38 expression on CD8 ϩ T cells is negatively correlated with age (2, 8, 11) and increased in HIV-infected children in comparison to HIV-uninfected age-matched controls (1,4,5,8,9). These findings are consistent with CD38 being a marker of immaturity and immune activation.…”

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy

“…As opposed to what occurs in adults, these results suggest that CD38 is a marker of cell immaturity rather than cell activation in CD4 + T cells in children [37,38]. Finding that its expression is high in naive CD4 + T cells [39], that it decreases over time [40] and that it increases in CD4 + T cells during immune reconstitution [37,38] all support this concept. Besides representing a marker of cell immaturity, CD38 in CD4 + T cells is likely to have multiple functional activities [37].…”

Interleukin-6 Release by Cultured Peripheral Blood Mononuclear Cells Inversely Correlates with Height Velocity, Bone Age, Insulin-like Growth Factor-I, and Insulin-like Growth Factor Binding Protein-3 Serum Levels in Children with Perinatal HIV-1 Infection

“…Liver disease was defined as previously reported (12 Interleukin-6 in vitro release. As previously described (3,4), PBMC were separated from EDTAtreated blood by centrifugation over Ficoll-Hypaque (␦ 1.077 g/cm 3 ; Pharmacia Biotech, Uppsala, Sweden) and resuspended at 10 6 cells/mL in RPMI 1640 (GIBCO Laboratories, Grand Island, NY) containing 0.5% penicillin, 0.5% streptomycin, 1% glutamine. Viable cell numbers were determined by trypan blue exclusion.…”