IL-21 Receptor Levels Associated With HIV-1 Viral Load and Disease Severity

Lab equipment centrifuging blood. Concept image of a blood test.3d rendering.Lab equipment centrifuging blood. Concept image of a blood test.3d rendering.
Researchers examined the expression of IL-21 receptor during HIV-1 infection and its role in HIV-1-specific CD8+ T cell maintenance and subsequent viral control.

Expression of the receptor for interleukin-21, a key cytokine for maintaining proper CD8+ T-cell function during acute HIV-1 infection, was significantly associated with HIV-1 viral load and disease progression, according to the results of a retrospective study published in AIDS.

Investigators collected peripheral blood mononuclear cell (PBMC) samples from 20 HIV-1-positive volunteers, 11 of whom were previously enrolled in the IAVI Protocol C, a longitudinal natural infection cohort study that followed participants for up to 7 years after early HIV infection. The investigators compared available plasma viral load data for HIV-1-positive volunteers with levels of interleukin-21 receptor (IL-21R) on CD8+ T cells to determine a correlation between the 2 factors. They used PBMC samples from a blood bank for 8 HIV-1-negative healthy individuals as control group samples.

The investigators employed flow cytometry to analyze IL-21 and IL-7 expression and enzyme-linked immunosorbent assay (ELISA) to measure plasma IL-21. To analyze expression on virus-specific CD8+ T cells, all 20 HIV-1-positive samples were stimulated with CMV and HIV-1 peptide pools prior to flow cytometry, followed by gating on the total antigen-specific CD8+ T cells.

HIV-1-positive donors had a significantly higher frequency of IL-21R on CD8+ T cells vs control group samples (P =.0256), with no significant difference in expression on CD4+ T cells. When stratified by CD8+ and CD4+ T-cell subpopulations, central memory and effector memory cells in HIV-1-positive donors had significantly higher levels of IL-21R expression vs control group samples (P =.0055 and P =.0487, respectively).

There was no significant difference in IL-7R or IL-21R expression on stimulated CD8+ T cells in HIV-1-positive samples vs unstimulated control group samples.

The investigators did not find a significant relationship between HIV-1 viral load and expression of IL-21R on the total CD8+ T cells with a Spearman’s correlation test. However, there was a positive correlation when investigators conducted an analysis on the HIV-1-specific CD8+ T cell population (P =.0152, r =.06667).

In the 11 HIV-1-positive volunteers from the IAVI Protocol C study, the investigators found a trend of increasing IL-21R expression on CD8+ T cells and decreasing plasma IL-21R with worsening disease. These donors also had a significant inverse correlation between plasma IL-21 and IL-21R expression on HIV-specific CD8+ T cells (P =.0440, r = -0.6273).

“We suggest that IL-21R could be a marker of disease progression for functional subsets of CD8+ T cells in HIV-1 infection,” the study authors wrote.


Dalel J, Ung SK, Hayes P, et al, IAVI Protocol C investigators list. HIV-1 infection and the lack of viral control are associated with greater expression of interleukin-21 receptor on CD8+ T cells. AIDS. 2021;35(8):1167-1177. doi:10.1097/QAD.0000000000002864