The expansion of T follicular helper (Tfh) cells correlates with disease progression in human and murine systemic lupus erythematosus (SLE). Unfortunately, there are no therapies to deplete Tfh cells. Importantly, low-dose rIL-2-based immunotherapy shows potent immunosuppressive effects in SLE patients and lupus-prone mice, primarily attributed to the expansion of regulatory T cells (Tregs). However, IL-2 can also inhibit Tfh cell differentiation. In this study, we investigate the potential of low-dose rIL-2 to deplete Tfh cells and prevent autoantibody responses in SLE. Our data demonstrate that low-dose rIL-2 efficiently depletes autoreactive Tfh cells and prevents autoantibody responses in lupus-prone mice. Importantly, this immunosuppressive effect was independent of the presence of Tregs. The therapeutic potential of eliminating Tfh cells was confirmed by selectively deleting Tfh cells in lupus-prone mice. Our findings demonstrate the critical role of Tfh cells in promoting autoantibody responses and unveil, (to our knowledge), a novel Treg-independent immunosuppressive function of IL-2 in SLE.
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