Effect of Low-Dose IL-2 Immunotherapy on Frequency and Phenotype of Regulatory T Cells and NK Cells in HIV/HCV-Coinfected Patients

Abstract

We evaluated the effect of low-dose IL-2 therapy (daily 1.2 MIU/m², subcutaneously) on the number and phenotype of regulatory T cells (T_regs) and natural killer (NK) cells in HIV/HCV-coinfected patients taking antiretroviral therapy. The frequency and phenotype of circulating T_regs (defined as CD3⁺ CD4⁺ CD25^high or CD3⁺ CD4⁺ FOXP3⁺) and NK cells (CD3⁻ CD16⁺/CD56⁺) were evaluated at baseline and after 12 weeks of treatment. The expression of CD25, CTLA-4, and granzymes A and B by CD4⁺ FOXP3⁺ cells, as well as the expression of KIR receptors (NKB1, CD158a, and NKAT2) on NK cells, was evaluated. Low doses of IL-2 resulted in the augmented frequency and absolute number of T_regs in coinfected individuals. FOXP3 levels per cell as well as augmented CD25 and CTLA-4 expression by T_regs suggested that IL-2 may lead to both expansion and activation of T_regs, although changes in the proportion of CD4⁺ FOXP3⁺ cells were not associated with changes in HCV viral load and CD4⁺ cells between baseline and week 12. NK cell frequency also increased after IL-2 therapy. Interestingly, the pattern of expression of KIR receptors was changed by IL-2 treatment, since the frequency of NK cells expressing NKB1 augmented whereas the frequency of NK expressing CD158a and NKAT2 decreased.