Differential loss of invariant natural killer T cells and FoxP3⁺ regulatory T cells in HIV-1 subtype A and subtype D infections

Abstract

HIV-1 subtype D is associated with faster disease progression compared with subtype A. Immunological correlates of this difference remain undefined. We investigated invariant natural killer T (iNKT) cells and FoxP3⁺ regulatory T cells (Tregs) in Ugandans infected with either subtype. Loss of iNKT cells was pronounced in subtype D, whereas Tregs displayed more profound loss in subtype A infection. The iNKT cell levels were associated with CD4 T-cell interleukin-2 production in subtype A, but not in D, infection. Thus, these viral subtypes are associated with differential loss of iNKT cells and Tregs that may influence the quality of the adaptive immune response.

FIGURE 1

iNKT cells and Treg cells in HIV-1 subtype A and D infection. Contour plots illustrating the gating strategy used to identify iNKT cells (A) and CD4+CD25+FoxP3+CD127− Treg cells (C). Box and Whisker plots showing the median and 10th–90th percentiles of iNKT cells (B) and Tregs (D) in HIV-1 negative and HIV-1 subtype A and D infected subjects. Statistically significant differences between groups were determined with non-parametric one-way ANOVA test. *** p < 0.001; ns = non-significant. Expression of IL-2 (E) and TNFα (F) alone, or triple-expression of IL-2, TNFα and IFNγ (G) by CD4 T cells correlates directly with the levels of iNKT cells in HIV-1 subtype A infected participants after stimulation of cells with SEB. An inverse correlation is seen between the same parameters after stimulation with CMV peptide pool (H–J). Correlation analysis between groups was performed with Spearman’s rank correlation.