Prevention of murine acute graft-versus-host disease by recipient-derived TGFbeta1-treated dendritic cells

Acute graft-versus-host disease (GVHD) remains the major barrier to allogeneic bone marrow transplantation (allo-BMT). Evidence has accumulated that transforming growth factor beta1-treated dendritic cells (TGFbeta-DC), deficient in surface costimulatory molecules, inhibit alloantigen-specific T-cell responses and induce graft hyporeactivity. To analyze the effect of TGFbeta-DC on GVHD after allo-BMT, 5.0 x 10(6) recipient-derived TGFbeta-DC were injected into C57BL/6 (H-2b) with bone marrow-splenocyte grafts from major histocompatibility complex (MHC) disparate BALB/c mice (H-2d). Survival analysis showed TGFbeta-DC cotransplantation resulted in significant prolongation of allograft survival, namely a mean survival time (MST) of 44.3 +/- 4.5 days, versus the untreated MST of 9.5 +/- 0.6 days (P < .01). However, mature DC aggravated the GVHD with an MST of 6.6 +/- 0.6 days (P < .01). In addition, the third-party C3H-derived TGFbeta-DC did not enhance the survival rate (MST = 9.7 +/- 0.5 days). Furthermore, serum IFN-gamma, IL-12, and IL-18 levels in TGFbeta-DC cotransplanted mice were reduced compared with untreated BMT hosts, while serum IL-10 levels were not changed. These results suggest that TGFbeta-DC cotransplantation may attenuate the severity of GVHD after BMT.