Immunotargeting of T Follicular Helper (TFH) Cells for SLE Treatment

Abstract

Abstract T follicular helper (TFH) cells promote antibody (Ab) responses by providing both survival and differentiation signals to B cells. As such, the expansion of self-reactive TFH cells contributes to auto-Ab production and correlates with disease severity in SLE. Importantly, blockade of TFH activity prevents auto-Ab production and disease progression in lupus-prone mice. Thus, TFH cells have been suggested as a target for treating SLE. Unfortunately, there are currently no therapies to selectively deplete TFH cells in vivo. We have previously identified IL-2 as a critical factor that suppresses TFH cell responses in vivo. In agreement with its negative role in TFH cell development, we show here that low-dose recombinant IL-2 (rIL-2) treatment prevents self-reactive TFH cell responses in lupus-prone mice. Importantly, this effect is independent of TREGS. Thus, our results demonstrate a novel immunosuppressive function of IL-2 that is independent of its role in regulatory T cell homeostasis. In addition, we demonstrate that rIL-2 can be targeted to TFH cells by adding an IL-6 blockade. Altogether, our data suggest that TFH cell suppression following low-dose IL-2 treatment is a significant mechanism underlying the immunosuppressive effects of low-dose rIL-2 immunotherapies.