Navegando por Palavras-chave "Rejection"

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    Experimental model for composite tissue allotransplantations
    (Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia, 2004-12-01) Ferreira, Lydia Masako [UNIFESP]; Ferreira, Luiz Roberto Kobuti; Universidade Federal de São Paulo (UNIFESP); University of São Paulo
    In homologous transplantation or allotranplantation of limbs, the great tissue diversity causes variability in the rejection process and, consequently, its immunology is very complex. Thus, limb transplantation is the most used prototype of compound tissue transplantation among the protocols of experimental studies. Composite tissue allotransplantation represents the experimental model to study the homologous transplantation (from an individual to another) of vascularized, innervated musclecutaneous units, joints, bone or even the whole member. Groups of rats were undergone allogeneic hindlimb transplantation. The receptors were randomized and control groups were established as: Control Group A: Autograft controls (F344 rats had its limbs reimplanted) and no immunosuppressive therapy. Control Group B: Allograft controls (BN rats limbs were transplanted to F344). Composite tissue homotransplantation allows the inclusion of innervated muscle-cutaneous units, joint and bone or even the hole limb, is considerably applicable in cases of congenital absence or deformity, trauma or greater resection due to malignant tumor. For many complex deformities, these transplantations would allow a more precise reconstruction than the current reconstruction techniques.
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    Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection
    (Associação Brasileira de Divulgação Científica, 2001-06-01) Shulzhenko, Natalia [UNIFESP]; Morgun, Andrey [UNIFESP]; Franco, Marcello Fabiano de [UNIFESP]; Souza, Marcia Marcelino de [UNIFESP]; Almeida, Dirceu Rodrigues de [UNIFESP]; Diniz, Rosiane Viana Zuza [UNIFESP]; Carvalho, Antonio Carlos [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Gerbase-Lima, Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.
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    The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection
    (Hospital Clinicas, Univ São Paulo, 2012-01-01) Commodaro, Alessandra Goncalves [UNIFESP]; Pedregosa, Juliana Figueredo [UNIFESP]; Peron, Jean Pierre; Brandao, Wesley; Rizzo, Luiz Vicente; Bueno, Valquiria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert Einstein; Universidade de São Paulo (USP)
    OBJECTIVES: FTY720 modulates CD4(+)T cells by the augmentation of regulatory T cell activity, secretion of suppressive cytokines and suppression of IL-17 secretion by Th17 cells. To further understand the process of graft rejection/acceptance, we evaluated skin allograft survival and associated events after FTY720 treatment.METHODS: F1 mice (C57BL/6xBALB/c) and C57BL/6 mice were used as donors for and recipients of skin transplantation, respectively. the recipients were transplanted and either not treated or treated with FTY720 by gavage for 21 days to evaluate the allograft survival. in another set of experiments, the immunological evaluation was performed five days post-transplantation. the spleens, axillary lymph nodes and skin allografts of the recipient mice were harvested for phenotyping (flow cytometry), gene expression (real-time PCR) and cytokine (Bio-Plex) analysis.RESULTS: the FTY720 treatment significantly increased skin allograft survival, reduced the number of cells in the lymph nodes and decreased the percentage of Tregs at this site in the C57BL/6 recipients. Moreover, the treatment reduced the number of graft-infiltrating cells and the percentage of CD4(+) graft-infiltrating cells. the cytokine analysis (splenocytes) showed decreased levels of IL-10, IL-6 and IL-17 in the FTY720-treated mice. We also observed a decrease in the IL-10, IL-6 and IL-23 mRNA levels, as well as an increase in the IL-27 mRNA levels, in the splenocytes of the treated group. the FTY720-treated mice exhibited increased mRNA levels of IL-10, IL-27 and IL-23 in the skin graft.CONCLUSIONS: Our results demonstrated prolonged but not indefinite skin allograft survival by FTY720 treatment. This finding indicates that the drug did not prevent the imbalance between Tr1 and Th17 cells in the graft that led to rejection.
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    Jagged2-signaling promotes IL-6-dependent transplant rejection
    (Wiley-Blackwell, 2013-06-01) Riella, Leonardo Vidal [UNIFESP]; Yang, Jun; Chock, Susanne; Safa, Kassem; Magee, Ciara N.; Vanguri, Vijay; Elyaman, Wassim; Lahoud, Youmna; Yagita, Hideo; Abdi, Reza; Najafian, Nader; Pestana, Jose Osmar Medina [UNIFESP]; Chandraker, Anil; Harvard Univ; Universidade Federal de São Paulo (UNIFESP); Univ Massachusetts; Brigham & Womens Hosp; Juntendo Univ
    The Notch pathway is an important intercellular signaling pathway that plays a major role in controlling cell fate. Accumulating evidence indicates that Notch and its ligands present on antigen-presenting cells might be important mediators of T helper cell differentiation. in this study, we investigated the role of Jagged2 in murine cardiac transplantation by using a signaling Jagged2 mAb (Jag2) that activates recombinant signal-binding protein-J kappa. While administration of Jag2 mAb had little effect on graft survival in the fully allogeneic mismatched model BALB/c -> B6, it hastened rejection in CD28-deficient recipients. Similarly, Jag2 precipitated rejection in the bm12 -> B6 model. in this MHC class II-mismatched model, allografts spontaneously survive for >56 days due to the emergence of Treg cells that inhibit the expansion of alloreactive T cells. the accelerated rejection was associated with upregulation of Th2 cytokines and proinflammatory cytokine IL-6, despite expansion of Treg cells. Incubation of Treg cells with recombinant IL-6 abrogated their inhibitory effects in vitro. Furthermore, neutralization of IL-6 in vivo protected Jag2-treated recipients from rejection and Jagged2 signaling was unable to further accelerate rejection in the absence of Treg cells. Our findings therefore suggest that Jagged2 signaling can affect graft acceptance by upregulation of IL-6 and consequent resistance to Treg-cell suppression.
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    Rejeição corneana pós transplante de córnea: análise de dados do Banco de Olhos do Hospital São Paulo - Escola Paulista de Medicina
    (Conselho Brasileiro de Oftalmologia, 2000-02-01) Chalita, Maria Regina Catai [UNIFESP]; Diazgranados, Eileen Beatriz Mejia [UNIFESP]; Sato, Elcio Hideo [UNIFESP]; Branco, Bruno Castelo [UNIFESP]; Freitas, Denise de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: Among all grafts, corneal transplantation is the most commonly performed. Graft outcome is usually good, but some cases failure due to rejection can be observed.There are some well-known risk factors for corneal graft rejection. The purpose of this study is to analyze cases of corneal graft rejection in our Service focusing on peculiar risk factors. Methods: We analyzed 113 cases of penetrating keratoplas-ties performed in 1998. Cases of corneal graft rejection were evaluated in relation to preoperative diagnosis, existence of synechia, corneal vascularization, increased intraocular pressure, previous graft rejection, donor age, time of enu-cleation and preservation of the donor cornea and the surgeon's surgical experience. Results: We were able to identify 20 (17.69%) cases of graft rejection. Among these 9 had synechia, 4 corneal neovas-cularization, 8 increased intraocular pressure and 7 pre-vious graft rejection. Conclusions: Our results are in agreement with those of the literature. It seems that the surgeon's experience plays a role in corneal graft rejection. It is important to call attention to the fact that reference services handle difficult and more complicated cases which may be at a higher risk to rejection.
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    The role of CD8+ T cells during allograft rejection
    (Associação Brasileira de Divulgação Científica, 2002-11-01) Bueno, Valquiria [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.
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    Uso da microscopia digital para comparação de espessura entre córneas normais e rejeitadas ex-vivo: ênfase na Membrana de Descemet
    (Universidade Federal de São Paulo (UNIFESP), 2019-06-27) Tognon, Taise [UNIFESP]; Burnier Júnior, Miguel Noel Nascente [UNIFESP]; Sousa, Luciene Barbosa de [UNIFESP]; http://lattes.cnpq.br/2367491641205774; http://lattes.cnpq.br/8668472375424523; http://lattes.cnpq.br/4487521900423032; Universidade Federal de São Paulo (UNIFESP)
    Objective: To analyze and compare thickness measurements of corneal layers, especially the Descemet membrane (DM), in normal corneas and in failed grafts due to rejection (FGRs) using a digital microscopy method. Methods: An experimental, cross-sectional, and analytical study was performed at the Henry C. Witelson Ocular Pathology Laboratory (McGill University Health Center and Research Institute, Montreal/Canada). Slides of 25 normal human corneas and 40 FGRs were examined using a Philips Ultra Fast Scanner® and the associated software. The inclusion criteria adopted were samples diagnosed as normal corneas or FGRs, all specimens were from patients older than 18 years of age. Slides with corneal structures that could not be adequately visualized and/or whose donor epidemiological information could not be obtained were excluded from the study. On each slide, the thickness of the corneal layers was measured, with 2 central measurements, 2 measurements at the nasal periphery, and 2 measurements at the temporal periphery using perpendicular planes as reference. Results: There were differences between the normal and FGR groups in the means of the central thickness of the epithelium (p<0.001), the nasal and temporal stroma regions (p<0.001), and the DM in the nasal and temporal regions (p<0.001). Comparing the mean thicknesses of the different regions (central, nasal and temporal) of the DM in the same group, the central region of the DM in the normal corneas had a lower mean thickness than the two peripheral regions (p<0.001), a difference that did not occur in the FGR group. Conclusions: Normal corneas had a lower epithelium thickness in the central region than did corneas in the FGR group. In addition, the stroma and DM thickness of the nasal and temporal periphery was significantly higher in normal corneas than in those from the FGR group.