The balance between alloreactive donor T cells and regulatory lymphocytes is essential for GVHD prevention. (A) Allogeneic T cells are crucial in the development of GVHD. They secrete large amounts of proinflammatory Th1-biased cytokines such as IFN-γ, which results in further T-cell activation and expansion. In contrast, a Th2-directed immune polarization favors GVDH prevention. Accordingly, the imbalance of allogeneic T cells and immunomodulatory lymphocytes results in GVHD. (B) Schneidawind et al¹  demonstrate how the adoptive transfer of low numbers of CD4⁺ iNKT cells expands donor Tregs and yields a cytokine bias in favor of Th2 cytokines. This balance of immunostimulatory and immunosuppressive cell subsets can dampen GVHD.