RESUMEN
This retrospective study was conducted to examine whether the presence of Foxp3+ cells in biopsies of kidney transplants displaying early acute rejection (AR) predicted the outcome of the episode. Seventeen biopsies showing AR included in this study were obtained at 42 +/- 30 days after transplantation. Lesions were graded according to the Banff classification. Foxp3 staining was performed on paraffin-embedded sections with a monoclonal antibody after antigen retrieval. We evaluated relationships between the number and the location of Foxp3+ cells, the type of rejection, and the serum creatinine value at 1 year. Foxp3+ cells were detected in 11 of 17 biopsies with AR (9.5 +/- 13.3 cells/mm(2)). These elements were mixed with other interstitial inflammatory cells. Intraepithelial tubular Foxp3+ cells were seen in 9 biopsies (1.5 +/- 2.5 cells/mm(2)). Foxp3+ cells were associated with borderline lesions (25.5 +/- 22.4/mm(2)); type 1 AR (7.18 +/- 9/mm(2)) and type 2 AR (1.99 +/- 3.46/mm(2)). The average number of cells per field was not different in C4d(+) and C4d(-) AR (6 +/- 8.35 vs 8.5 +/- 14.7/mm(2)). Graft loss within the first year was higher among the group of recipients without Foxp3+ cells (3/6) than those with Foxp3+ cells (0/11). All AR with intraepithelial tubular Foxp3 cells had favorable outcomes. Foxp3 has been proposed as a relevant marker of CD4(+)CD25(+) regulatory T cells. This study showed that Foxp3+ cells can be detected in kidney transplant biopsies with AR. The absence of Foxp3+ cells, especially in epithelial tubular cells, might indicate a poor prognosis following an AR episode.
Asunto(s)
Factores de Transcripción Forkhead/análisis , Rechazo de Injerto/patología , Trasplante de Riñón/patología , Enfermedad Aguda , Adulto , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
The aim of this study was to determine the expression of transforming growth factor-beta (TGFbeta)-1 and type I TGFbeta-receptor on sequential biopsies from renal transplants with and without chronic allograft nephropathy. Twenty-four renal transplant recipients entered the study. They underwent sequential biopsies performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2 months) transplantation. Lesions were graded according to the criteria of the Banff classification. C4d was detected by fluorescence microscopy. Immunohistochemistry was performed in order to identify cells expressing TGFbeta-1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type 1 TGFbeta-receptor is expressed by tubular epithelial cells and smooth muscle cells in the media of arteries. In recipients with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial expression of both molecules was found in more patients at T2 than at T1 (42.8% vs 21.4%). In contrast, this pattern of expression remained stable or decreased over time in recipients with long-term normal transplants (group 2, n = 10). Furthermore, type 1 TGFbeta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group 1 and only in 4/9 (44.4%) of recipients in group 2. No relationship was noticed with regard to C4d deposits. These data suggest that the synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy. Further studies are in progress in order to quantify mRNA of both molecules with real-time polymerase chain reaction.
Asunto(s)
Receptores de Activinas Tipo I/genética , Trasplante de Riñón/patología , Receptores de Factores de Crecimiento Transformadores beta/genética , Factor de Crecimiento Transformador beta1/genética , Biopsia , Enfermedad Crónica , Estudios de Seguimiento , Humanos , Trasplante de Riñón/fisiología , Músculo Liso Vascular/inmunología , Músculo Liso Vascular/patología , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/patología , Proteínas Serina-Treonina Quinasas , Receptor Tipo I de Factor de Crecimiento Transformador beta , Circulación Renal , Factores de Tiempo , Urotelio/inmunología , Urotelio/patologíaRESUMEN
The aim of this work was to study cellular chimerism achieved in lymphoid tissues and production of antidonor lymphocyte antibodies after injection of splenic dendritic cells (DCs) from Fischer F344 rats to Lewis recipients, a model of chronic rejection. DCs isolated from the spleen expressed OX62 (95%), CD80 (70%), and CD86 (80%). Two doses of these nonplasmacytoid splenic DCs from Fischer rats (2 x 10(6) and 5 x 10(6)), which had been labeled ex vivo with a TRITC fluorochrome (PKH26), were injected to Lewis recipients. Using fluorescence microscopy TRITC positive cells were localized at day 15 and day 45 in frozen sections from spleen, thymus, mesenteric lymph nodes, heart, liver, kidney, and skin (n = 5 per group). Donor-specific antibodies were sought with flow cytometric crossmatches in serum samples taken at 7, 15, 30, and 45 days. TRITC-positive DCs were essentially localized in the spleen, the thymus, and lymph nodes of Lewis recipients. The majority of DCs were detected in the spleen (14.9 +/- 3.3 and 14.3 +/- 0.9 DCs/per high power field respectively at day 45). A significant number of DCs was also detected in the thymus and mesenteric lymph nodes at both times. Only some scattered TRITC-positive cells were observed in other organs. The number of DCs was stable over time and did not depend on the injected dose. A positive flow cytometric cross-match was observed at day 30 in all recipients independent of the injected dose. These data showed that 2 x 10(6) mature, nonplasmocytoid DCs from F344 rats injected to Lewis recipients induced stable chimerism in primary and secondary lymphoid organs and a humoral response to donor antigens.