Low-Dose Interleukin-2 Enhances Activated Suppressor Regulatory T Cells and CTLA-4 and HLA-DR Expression in Chronic...

Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood mononuclear cells from adults with laboratory-confirmed chronic chikungunya arthritis in Atlántico, Colombia. Cells were treated ex vivo with recombinant IL-2 or an IL-2/anti-IL-2 monoclonal antibody complex in the presence of CD2/CD3/CD28 stimulation beads, followed by flow cytometric assessment of effector T cells and Tregs. Low-dose IL-2 treatments ex vivo did not increase total Treg frequency but selectively increased activated suppressor Tregs while decreasing activated T effector cells, enhancing Treg CTLA-4 and HLA-DR expression, and reducing Ki67 expression in effector T cells. IL-2 complex treatment decreased cytokine-secreting Tregs, and IL-10 and TGF-β were not associated with IL-2 treatment status or with Teff/Treg balance, suggesting limited utility as pharmacodynamic biomarkers of low-dose IL-2 treatments. These findings support the use of activated suppressor Tregs, Treg CTLA-4, and HLA-DR expression as candidate biologic endpoints for evaluation in future trials of low-dose IL-2 in chikungunya arthritis.