ObjectivesTo clarify the effects of IL-21 on cytotoxic effect of SHIV-specific CD8⁺ T cells. Methods Peripheral blood samples were collected from 16 SHIV-infected rhesus monkeys. Real-time fluorescence quantitative RT-PCR assay was used to determine virus load for SHIV RNA, and absolute amount of CD8⁺ T cells were assessed by flow cytometry. The expression of IL-21R, perforin, and CD107a of the CD8⁺ T cells in vitro was assayed by flow cytometry after IL-21 stimulation. CD107a mobilization assay was used to measure the degranulation of CD8⁺ T cells. ResultsIn vivo study indicated a negative correlation between the virus load and the absolute number of CD8⁺ T cells. Compared with the medium control, the expression of IL-21R on the surface of CD8⁺ T cells was significantly increased. Moreover, percentages of both CD107a+ CD8⁺ T cells and perforin+ CD8⁺ T cells were higher than those of the control. ConclusionsAdministration of IL-21 upregulates cytotoxic effect of peripheral CD8⁺ T cells in SHIV-infected rhesus monkeys.