387 Background. Graft vasculopathy, the hallmark of chronic rejection, involves early immune and later sclerotic processes. TGF-β1 is upregulated during chronic rejection. While pro-arteriosclerotic properties of TGF-β1 are well established, far less is known about the immunosuppressive effects of TGF-β1 on graft vasculopathy. Methods & Results. To create an allograft microenvironment with selective disruption of TGF-β1 in infiltrating immune cells, we studied grafts placed into TGF-β1-deficient recipients using our heterotopic, vascularized transplant model in mice. Graft vasculopathy was studied in 55 day grafts from recipients treated with anti-CD4/8 for 30 days. We compared wild type donor hearts (CBA) placed into heterozygous TGF-β1-deficient recipients (C57BL6, TGF-β1+/-, n=7) with those placed into wild type recipients (C57BL6, WT, n=11). Computer-assisted vessel analysis was used to assess severity of luminal occlusion (Verhoeff) in all vessels (n=173) as well as quantitate perivascular fibrosis (Trichrome) and neointimal α-actin-smooth muscle cell expansion in a representative subset of vessels (n=40). We found a significant increase in severity of luminal occlusion in grafts from TGF-β1 recipients (67.8±14.7%) compared to WT recipients (47.4±13.7%, p=0.003). Quantitatively, the neointima was composed of similar contributions of CD45- and α-actin positive cells. Quantitatively, perivascular fibrosis (perivascular collagen-positive area/vessel area: TGF-β1 0.42±0.24, WT 0.2±0.61) and myointimal expansion (neointimal α-actin-positive area/neointimal area: TGF-β1 0.22±0.09, WT 0.24±0.11) were comparable in both groups. To determine whether immune cell-deficiency of TGF-β1 alters the allograft cytokine activation pattern, we measured corrected cytokine transcript levels using 32P RT-PCR. We found that grafts from TGF-β1 had significantly increased mean transcript levels for interferon-γ (p=0.006) and interleukin-2 (p=0.005) without changes in interleukin-4 and -5. Conclusion. Immune sources of TGF-β1, when present, attenuate the development of graft vasculopathy without affecting perivascular fibrosis or myointimal expansion. These anti-arteriosclerotic properties coincide with shifts in the allograft cytokine activation pattern. TGF-β1-deficiency produces an immune deviation towards a Th1 pattern(interferon-γ, interleukin-2) which promotes vascular remodeling. Hence, TGF-β1 may be useful to attenuate immune processes that lead to graft vasculopathy.