CD8+ T-cell interleukin-7 receptor alpha expression as a potential indicator of disease status in HIV-infected children

Abstract

Background: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease.

Methods: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status.

Results: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers.

Conclusions: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression.

Figure 1. Gating strategy for the identification of CD127 expression on CD8+ T cells.

Lymphocytes were selected in a forward scatter height (FSC-H) versus side scatter height (SSC-H) plot. T cells were then selected by gating on CD3+ cells. A–C. Pattern of CD127 expression on CD8+ T-cells in the peripheral blood of 3 of our HIV-infected children with differing CD4+ T-cell frequencies. Results from 3 individual children are shown, with respective CD8+ lymphocyte frequencies of 3% (A), 23% (B) and 46% (C). The values in brackets represent CD127 expression as a frequency of total CD8+ T cells. Results shown are gated on CD3+ T cells.

Figure 2

A–B. Association between CD8+ T-cell expression of CD127 (A.) and of CD38 (B.) and CD4+ lymphocyte frequency, in 48 HIV-infected children. A Spearman test was used to assess correlations. C–D. Relationship of CD8+ T-cell expression of CD127 (C) and of CD38 (D) with degree of immunosuppression, as categorized by current CD4+ lymphocyte frequency. Mann Whitney test was used to assess differences between the groups.

Figure 3

A–B. Association between CD8+ T-cell expression of CD127 (A.) and of CD38 (B.) and plasma HIV viral load, in 48 HIV-infected children. The lower limit of detection of the plasma HIV assay was 400 copies/mL. A Spearman test was used to assess correlations. C.–D. Relationship of CD8+ T-cell expression of CD127(C) and of CD38 (D) with degree of virologic control, as categorized by the plasma HIV viral load. Mann Whitney test was used to assess differences between the groups.

Figure 4

A–B. Relationship between CD8+ T-cell expression of CD127 (A), and of CD4+ T-cell frequency (B), with “current” CDC clinical disease category, in 48 HIV-infected children. ”Current” HIV clinical stage refers to a revised CDC classification, based on symptomatic disease at the time of study enrollment. Mann Whitney test was used to assess differences between the groups. C.–D. Association between height for age z-score (C) and weight for age z-score (D) and CD8+ T-cell expression of CD127. A Spearman test was used to assess correlations.