Immunologic. The underlying mechanisms leading to HSC coexistence have been the object of intense investigation, with no clear answer yet emerging. Conditioning, toxicity, GVHD, and other factors do not seem to play a role. Serafini et al37 showed that the alloreactive T-cell clones of both host and donor origins, isolated from the peripheral blood of the mixed chimera patients, could function as partially effector T cells reactive against host or donor alloantigens. Moreover, these cells were partially regulatory T cells with a cytokine secretion profile typical of type 1 regulatory T cells. Importantly, the regulatory T-cell clones, both donor and host derived, were able to inhibit cytokine production and proliferation of effector cells of either donor or host origin, suggesting a contribution by these regulatory T cells to the maintenance of persistent mixed chimerism in vivo. These data provide new insights into the mechanisms of peripheral tolerance and may pave the way for cellular therapy trials following HSC transplantation in nonmalignant diseases.