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Indirect Pathways (indirect + pathway)
Selected AbstractsGraft rejection mediated by CD4+ T cells via indirect recognition of alloantigen is associated with a dominant Th2 responseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Keri Csencsits Abstract CD4+ T cells that respond to indirectly presented alloantigen have been shown to mediate chronic rejection, however, the role of the indirect pathway in acute rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6 mice were depleted of CD8+ T cells and transplanted with class II transactivator (CIITA)-deficient cardiac allografts, which cannot directly present class II alloantigens to CD4+ T cells. In this manner, the rejection response by CD4+ cells was forced to rely upon the indirect recognition pathway. When not depleted of CD8+ cells, both BALB/c and C57BL/6 mice rejected CIITA,/, allografts and a polarized Th1 response was observed. In contrast, when BALB/c recipients of CIITA,/, allografts were depleted of CD8+ T cells, the grafts were acutely rejected and a strong Th2 response characterized by eosinophil influx into the graft was observed. Interestingly, CD8-depleted C57BL/6 recipients of CIITA,/, allografts did not acutely reject their transplants and a Th2 response was not mounted. These findings indicate that CD4+ T cells responding to indirectly presented alloantigens mediate graft rejection in a Th2-dominant manner, and provide further evidence for the role of Th2 responses in acute graft rejection. [source] A pathway through interferon-, is the main pathway for induction of nitric oxide upon stimulation with bacterial lipopolysaccharide in mouse peritoneal cellsFEBS JOURNAL, Issue 19 2003Motohiro Matsuura Production of nitric oxide (NO) in response to bacterial lipopolysaccharide (LPS) was investigated using cultures of mouse peritoneal exudate cells (PEC) and the macrophage cell line RAW264.7. In the presence of anti-(interferon-,) (IFN-,), NO production was markedly suppressed in the PEC culture but not in the RAW264.7 culture. In the PEC culture, LPS induced both IFN-, production and activation of IFN response factor-1, which leads to the gene expression of inducible NO synthase, but neither was induced in the culture of RAW264.7 cells. In addition to anti-(IFN-,), antibodies against interleukin (IL)-12 and IL-18 showed a suppressive effect on LPS-induced NO production in the PEC culture, and these antibodies in synergy showed strong suppression. Stimulation of the PEC culture with IL-12 or IL-18 induced production of IFN-, and NO, and these cytokines, in combination, exhibited marked synergism. Stimulation of the culture with IFN-, induced production of NO, but not IL-12. The macrophage population in the PEC, prepared as adherent cells, responded well to LPS for IL-12 production, but weakly for production of IFN-, and NO. The macrophages also responded well to IFN-, for NO production. For production of IFN-, by stimulation with LPS or IL-12 + IL-18, nonadherent cells were required in the PEC culture. Considering these results overall, the indirect pathway, through the production of intermediates (such as IFN-,-inducing cytokines and IFN-,) by the cooperation of macrophages with nonadherent cells, was revealed to play the main role in the LPS-induced NO production pathway, as opposed to the direct pathway requiring only a macrophage population. [source] Effects of repeated burning on species richness in a Florida pine savanna: A test of the intermediate disturbance hypothesisJOURNAL OF VEGETATION SCIENCE, Issue 1 2000Brian Beckage Wunderlin (1982) except for Aristida beyrichiana; which follows Peet (1993). Vouchers for each species were collected and deposited at the University of Central Florida herbarium Abstract. We studied the effect of burning frequency on the density and species richness of understory flowering stems in a Florida sandhill. Flowering stems were censused weekly for 54 weeks in six sites that had been burned one to six times in the previous 16 years. We concurrently measured overstory characteristics such as species composition, density and basal area. We used maximum likelihood and Akaike's Information Criterion to compare linear, quadratic, saturating, and null models of community response to repeating burning. We did not find a relationship between species richness, diversity or flowering stem density and fire frequency. Tree density was related to fire frequency and may represent an indirect pathway for fire effects on understory characteristics. While we found no support for the Intermediate Disturbance Hypothesis, an analysis of our experimental design indicated that we had low statistical power. We develop the hypothesis that a saturating model of response to fire best describes understory species richness in our system. We test this hypothesis using the most extensive published fire data set we are aware of and find support for a saturating model. [source] Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditionsMAGNETIC RESONANCE IN MEDICINE, Issue 1 2009Ana F. Soares Abstract Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed rats. Following 2H2O administration and overnight feeding, the livers were removed and glycogen 2H-enrichment was measured by 2H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 ± 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% ± 4% for control rats,similar to values from healthy, meal-fed humans. In STZ-treated rats, the indirect pathway contribution was significantly higher (68% ± 4%, P < 0.05 vs. controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from 2H2O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients. Magn Reson Med 61:1,5, 2009. © 2008 Wiley-Liss, Inc. [source] Differential Role of Naïve and Memory CD4+ T-Cell Subsets in Primary AlloresponsesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Golshayan The T cell response to major histocompatibility complex (MHC) alloantigens occurs via two main pathways. The direct pathway involves the recognition of intact allogeneic MHC:peptide complexes on donor cells and provokes uniquely high frequencies of responsive T cells. The indirect response results from alloantigens being processed like any other protein antigen and presented as peptide by autologous antigen-presenting cells. The frequencies of T cells with indirect allospecificity are orders of magnitude lower and comparable to other peptide-specific responses. In this study, we explored the contributions of naïve and memory CD4+ T cells to these two pathways. Using an adoptive transfer and skin transplantation model we found that naive and memory CD4+ T cells, both naturally occurring and induced by sensitization with multiple third-party alloantigens, contributed equally to graft rejection when only the direct pathway was operative. In contrast, the indirect response was predominantly mediated by the naïve subset. Elimination of regulatory CD4+CD25+ T cells enabled memory cells to reject grafts through the indirect pathway, but at a much slower tempo than for naïve cells. These findings have implications for better targeting of immunosuppression to inhibit immediate and later forms of alloimmunity. [source] Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditionsMAGNETIC RESONANCE IN MEDICINE, Issue 1 2009Ana F. Soares Abstract Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum-fed rats. Following 2H2O administration and overnight feeding, the livers were removed and glycogen 2H-enrichment was measured by 2H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 ± 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% ± 4% for control rats,similar to values from healthy, meal-fed humans. In STZ-treated rats, the indirect pathway contribution was significantly higher (68% ± 4%, P < 0.05 vs. controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from 2H2O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients. Magn Reson Med 61:1,5, 2009. © 2008 Wiley-Liss, Inc. [source] Direct and indirect pathways in levodopa-induced dyskinesia: A more complex matter than a network imbalance,MOVEMENT DISORDERS, Issue 11 2010Veronica Ghiglieri PhD No abstract is available for this article. [source] Direct and indirect pathways between adult attachment style and marital satisfactionPERSONAL RELATIONSHIPS, Issue 2 2002Steven A. Meyers We explored direct, mediated, and moderated associations between adult attachment style and marital satisfaction using a community-based sample of 73 married women. Continuous ratings of secure, avoidant, and ambivalent attachment styles were related to levels of marital satisfaction. However, psychological distress mediated the association between secure attachment and marital satisfaction, and social support mediated the relation between avoidant attachment and marital satisfaction. In addition, psychological distress moderated the relation between both secure and avoidant attachment styles and marital satisfaction. [source] ORIGINAL ARTICLE: The Persistence of Paternal Antigens in the Maternal Body is Involved in Regulatory T-Cell Expansion and Fetal-Maternal Tolerance in Murine PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Maria Laura Zenclussen Citation Zenclussen ML, Thuere C, Ahmad N, Wafula PO, Fest S, Teles A, Leber A, Casalis PA, Bechmann I, Priller J, Volk H-D, Zenclussen AC. The persistence of paternal antigens in the maternal body is involved in regulatory T-cell expansion and fetal-maternal tolerance in murine pregnancy. Am J Reprod Immunol 2010; 63: 200,208 Problem, Mammalian pregnancy is a state of immunological tolerance and CD4+ CD25+ regulatory T cells (Treg) contribute to its maintenance. Knowing that Treg act in an antigen-specific way during pregnancy, we hypothesized that they are generated after maternal immune cells encounter paternal antigens. Method of study, We mated wild type females with transgenic green fluorescent protein (GFP) males in an allogenic setting and killed them on different days of pregnancy. Results, Presence of paternal and maternal MHC class II+ cells in vaginal lavage on day 0.5 of pregnancy was confirmed. Thus, antigen presentation may take place early during pregnancy in the periphery either by the direct or indirect pathways. Foxp3+ cells known to have regulatory activity could be detected on day 2 of pregnancy in lymph nodes and shortly after implantation at the fetal-maternal interface. Conclusion, Our data suggest that paternal antigens are processed early during pregnancy, which leads to the generation of Treg. The continuous release of placental antigens into the maternal circulation allows the maintenance of a Treg population which is specific for paternal antigens and mediates tolerance toward the semi-allogeneic fetus until the time point of birth. [source] Preferential Priming of Alloreactive T Cells with Indirect ReactivityAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009T. V. Brennan The relative contributions of the direct and indirect pathways in alloimmune responses have not been fully elucidated. We report a novel murine TCR transgenic system that can simultaneously track the CD4-direct (CD4-d), CD4-indirect (CD4-i) and CD8-direct (CD8-d) pathways after transplantation. Using this system, we have observed a profoundly greater proliferation of CD4-i T cells relative to CD4-d and CD8-d T cells after transplantation. Furthermore, a much larger proportion of CD4-i T cells attain an effector phenotype. We also analyzed endogenous, wild-type T cells using enzyme-linked immunospot analysis. In naïve mice, T cells with indirect reactivity were undetectable, but T cells with direct reactivity were abundant. However, 10 days after skin or heterotopic heart transplantation, CD4-i T cells comprised approximately 10% of the CD4+ response. Consistent with increased priming of the CD4-i pathway, we observed that the CD4-i T cells were further enriched in the effector cells migrating to the allograft and in memory-like T cells persisting after rejection. Thus, priming of the CD4-i pathway is favored after transplantation, allowing a rare population to rapidly become a major component of the CD4+ T-cell response in acute allograft rejection. The generalizability of this observation to other models remains to be determined. [source] Predicting the unexpected: using a qualitative model of a New Zealand dryland ecosystem to anticipate pest management outcomesAUSTRAL ECOLOGY, Issue 4 2009DAVID S. L. RAMSEY Abstract Pest management is expensive and there is often uncertainty about the benefits for the resources being protected. There can also be unintended consequences for other parts of the ecosystem, especially in complex food webs. In making decisions managers generally have to rely on qualitative information collected in a piecemeal fashion. A method to assist decision making is a qualitative modelling approach using fuzzy cognitive maps, a directed graphical model related to neural networks that can take account of interactions between pests and conservation assets in complex food webs. Using all available information on relationships between native and exotic resources and consumers, we generated hypotheses about potential consequences of single-species and multi-species pest control on the long-term equilibrium abundances of other biotic components of an ecosystem. We applied the model to a dryland ecosystem in New Zealand because we had good information on its trophic structure, but the information on the strength of species interactions was imprecise. Our model suggested that pest control is unlikely to significantly boost native invertebrates and lizards in this ecosystem, suggesting that other forms of management may be required for these groups. Most of the pest control regimes tested resulted in greater abundances of at least one other pest species, which could potentially lead to other management problems. Some of the predictions were unexpected, such as more birds resulting from possum and mouse control. We also modelled the effects of an increase in invasive rabbits, which led to unexpected declines of stoats, weasels, mice and possums. These unexpected outcomes resulted from complex indirect pathways in the food web. Fuzzy cognitive maps allow rapid construction of prototype models of complex food webs using a wide range of data and expert opinion. Their utility lies in providing direction for future monitoring efforts and generating hypotheses that can be tested with field experiments. [source] Pathways of stakeholder influence in the Canadian forestry industryBUSINESS STRATEGY AND THE ENVIRONMENT, Issue 6 2005Irene Henriques Abstract We draw on the stakeholder influence literature to propose and empirically test hypotheses regarding the direct and indirect pathways of perceived influence that stakeholders exercise within the domain of corporate sustainability. Our results allow us to examine the interaction between different types of stakeholder pressure and different types of stakeholder influence strategy. We show that stakeholders who do not control resources critical to the focal firm's operations are able to pressure a firm indirectly via other stakeholders on whose resources the firm is dependent. We contribute to the stakeholder perspective by showing how stakeholders who are affected by the focal firm's operations can enhance their salience via stakeholders who can affect the firm. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment. [source] Parents' Roles in Shaping Early Adolescents' Occupational AspirationsCHILD DEVELOPMENT, Issue 4 2001Kathleen M. Jodl Relations among dimensions of parenting and adolescents' occupational aspirations were examined in two specific domains: academics and sports. The sample consisted of 444 seventh graders, with approximately equal numbers of African American and European American males and females, from two-parent nondivorced families. Multiple measures were used as indicators of parents' values and behaviors, youths' values and beliefs, positive identification with parents, and adolescents' occupational aspirations. In the academic domain, parents' values predicted youths' values directly rather than indirectly through their behaviors. In contrast, fathers' behaviors mediated the relation between parents' and youths' values in the sports domain. Positive identification was directly related to adolescents' values (especially about academics); however, positive identification did not moderate the transmission of values from parent to child in either domain. Parents' values predicted adolescents' occupational aspirations via both direct and indirect pathways. Similar results were obtained for African American and European American males and females. These findings highlight the potential role of parents as socializers of achievement-related values, and, ultimately, adolescents' occupational visions of themselves in the future. [source] | |||||||||||||