Interleukin-2 significantly upregulates CD86 expression on T cells during cytokine therapy (131.35)

Abstract

Interleukin-2 (IL-2) is one of the most widely used cytokines in therapeutic applications, and its efficacy in the treatment of various cancers and chronic viral infections has been extensively tested. Several studies have focused on the impact of IL-2 on T-cell survival and proliferation. However, very few have focused on IL-2-induced phenotypic changes in T cells, although this is particularly relevant to cytokine therapy. To gain insight into this issue, we analyzed blood samples from patients receiving IL-2 therapy in order to elucidate the phenotype changes occurring in their T cells. A key finding was a marked increase in CD86 expression on CD4+ and CD8+ T cells. Detailed characterizations of the corresponding cytokine-induced CD86 expression profiles on T cells were obtained in subsequent in vitro experiments. We found that the IL-2-induced CD86 molecules are unable to provide costimulatory signals to antigen-specific T cells during activation. Moreover while these CD86 molecules shown to have no binding affinity for CD28 molecules, their binding affinity for the inhibitory molecule CTLA-4 remained intact. Therefore, it is likely that the IL-2-induced CD86 expression on T cells have a modulatory role on IL-2-induced inflammatory response and its related side effects.