RESUMEN
Although previous studies have demonstrated the efficient modulatory effects of ultraviolet radiation B (UVB) on cutaneous graft-versus-host disease (GVHD), most animal research on GVHD has been performed in murine models of acute GVHD. Here, we studied the preventive effect of UVB radiation on the occurrence of chronic sclerodermatous (Scl) GVHD in a murine model. Scl GVHD was induced by transplanting lethally irradiated BALB/c mice with B10.D2 bone marrow and spleen cells. Recipient mice were exposed to UVB before or after bone marrow and spleen cell infusion. Histological and clinical evaluation of GVHD was performed, in association with the characterization of epidermal Langerhans cells. UVB irradiation of recipients after, and more remarkably before, transplantation induced a decrease of Scl GVHD severity associated with epidermal Langerhans cells depletion. We conclude that UVB irradiation of recipient before or after transplantation has a preventive effect on cutaneous Scl GVHD and may represent an effective strategy for prevention of Scl GVHD.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/patología , Transfusión de Linfocitos , Esclerodermia Limitada/radioterapia , Esclerodermia Limitada/cirugía , Trasplante Homólogo/inmunología , Trasplante Homólogo/patología , Rayos Ultravioleta , Animales , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Inmunohistoquímica , Células de Langerhans/patología , Células de Langerhans/efectos de la radiación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Bazo/trasplanteRESUMEN
BACKGROUND: Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced-intensity conditioning transplantation (RICT), autoantibody production, and chronic GVHD (cGVHD)-related pathology. METHODS: Chimerism state, circulating anticardiolipin, and antidouble stranded DNA autoantibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model. RESULTS: We observed a novel association between mixed chimerism state, high levels of pathogenic IgG autoantibodies, and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of autoantibodies. CONCLUSION: Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Células Madre Hematopoyéticas/fisiología , Quimera por Trasplante/inmunología , Animales , Autoanticuerpos/sangre , Autoinmunidad , Trasplante de Médula Ósea/patología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Interferón gamma/sangre , Interleucina-13/sangre , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Cellular cardiomyoplasty is a promising approach to improve postinfarcted cardiac function. The differentiation pathways of engrafted mesenchymal progenitor cells (MPCs) and their effects on the left ventricular function in a rat myocardial infarct heart model were analyzed. METHODS AND RESULTS: A ligation model of left coronary artery of Lewis rats was used. MPCs were isolated by bone marrow cell adherence. Seven days after ligation, MPCs labeled with 4',6-diamidino-2'-phenylindole were injected into the infarcted myocardium (n=8). Culture medium was injected in the infarcted myocardium of control animals (n=8). Thirty days after implantation, immunofluorescence studies revealed some engrafted cells expressing a smooth muscle phenotype (alpha SM actin+), as similarly observed in culture. Other engrafted cells lost their smooth muscle phenotype and acquired an endothelial phenotype (CD31+). Furthermore, vessel density was augmented in the MPC group in comparison with the control group. After 30 days, echocardiography showed an improvement on left ventricular performance in the MPCs compared with the control group. CONCLUSIONS: In vivo administration of syngenic MPCs into a rat model of myocardial infarcted heart was safety demonstrated. Some engrafted cells appeared to differentiate into endothelial cells and loss their smooth muscle phenotype. MPC engraftment might to contribute to the improvement on the cardiac function in such a setting.