Summary. Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (a-SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and a-SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and a-SMA) and also to double stain for CD34 and a-SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury.

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Summary:Activation of donor T cells is required for the development of graft-versus-host disease (GVHD), a major complication of bone marrow transplantation. We investigated a murine model of GVHD across major and minor histocompatibility barriers. BALB/c recipients were lethally irradiated and transplanted with 10 7 bone marrow and 5 ؋ 10 6 spleen cells from C57BL/6 donors. There were two separate phases of clinical disease. The first phase was most severe on day 7 after transplant. Weight and condition improved until day 12 and then a second phase of clinical GVHD commenced, which persisted until euthanasia. IL-2 mRNA expression, as a measure of T cell activation, was determined by quantitative PCR. The two phases of clinical GVHD were preceded by two separate peaks of IL-2 mRNA in the spleen. Host MHC class II + cells became undetectable by flow cytometry 7 days after transplantation, whereas donor MHC class II + cells increased during the first 9 days after transplantation. Removal of donor MHC class II + cells from the graft had no effect on the first phase. Possible roles for host and donor antigenpresenting cells (APC) in the two phases of the disease are discussed. Bone Marrow Transplantation (2002) 29, 151-158. DOI: 10.1038/sj/bmt/1703328 Keywords: graft-versus-host; MHC; antigen presentation; transplantation; cytokines Acute graft-versus-host disease (GVHD) remains the most significant obstacle to successful allogeneic BMT or peripheral blood stem cell transplantation for leukemia and other conditions. In MHC-matched unrelated donor transplants, acute GVHD of grade II or above occurs in up to twothirds of cases. 1 Acute GVHD has a complex pathophysiology which can involve wasting, diarrhea, skin and gut lesions and liver damage. 2 T cell activation in response to