Selective Regulation of CD8 T Cell Immune Function by IL-21 in HIV Infected Individuals

Background

HIV infection is associated with skewed maturation of CD8 T cells, accumulation of cells in pre-effector stages and impaired effector function. Two g-chain signaling cytokines, IL-21 and IL-15, are known to enhance IFN-g in antigen-specific CD8T cells in humans and murine models and to synergize with each other. This study investigated IL-21 effects on CD8 T cells of HIV infected subjects.

Methods

Fresh peripheral blood mononuclear cells of healthy donors (n = 7) and HIV+ patients (n = 10, CD>4200 mm3, VL<200 copies/ml) were cultured for 5 days with IL-21 (50 ng/ml) or IL-15 (50 ng/ml) and analyzed for the expression of intracellular perforin and cellular proliferation (CFSE-dye dilution) in maturation subsets of CD8 T cells based on expression of CD45RA/CD62L.

Results

By itself, IL-21 addition significantly increased perforin, particularly in effector memory (EM) CD8 T cells (62% ± 8 vs 27% ± 7) and proliferation of this subset (10% ± 3 vs 0.5% ± 0.1) only in HIV subjects. In contrast, IL-15 upregulated perforin in central memory and EM CD8 T cells and induced proliferation in all CD8 maturation stages in all subjects.

Conclusion

IL-21 selectively augments EM CD8 T cell proliferation and perforin in HIV+ individuals, whereas IL-15 induces pan CD8 T cell activation in both, healthy and HIV+ individuals. The EM CD8 T cells of HIV+ patients are more responsive to IL-21 than healthy control cells.