Cellular therapies including MSC, Treg, NKT-, and B cell targeting. The left panel highlights the central role of various cell types including B and NKT cells for effector T-cell activation during GVHD. In this GVHD favoring scenario NKT-cell–derived IFN-γ and B cells function as T-cell activators, while Treg expansion is suppressed. The right panel depicts potential strategies how this processes can be manipulated to favor a more tolerogenic environment. Adoptive transfer of in vitro generated or donor-derived Treg, MSC or NKT cells either directly inhibits effector T-cell activation and expansion, or indirectly tips the balance toward a tolerogenic milieu by inducing Treg expansion. Moreover, cellular compartments known to be involved in the activation of alloreactive T cells, such as B cells can be depleted by monoclonal antibodies directly targeting B cells (ie rituximab). Therapeutic strategies currently in clincial testing are shown in brown, preclinical concepts in red. MSC indicates mesenchymal stem cell; Treg, regulatory T-cell; NKT, natural killer T-cell; BC, B cell; DC, dendritic cell; TC, T-cell; and SLO, secondary lymphoid organ.