The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Shimon Sakaguchi - One of the best experts on this subject based on the ideXlab platform.
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naturally arising foxp3 expressing cd25 cd4 regulatory t cells in Immunological Tolerance to self and non self
Nature Immunology, 2005Co-Authors: Shimon SakaguchiAbstract:Naturally arising Foxp3-expressing CD25 + CD4 + regulatory T cells in Immunological Tolerance to self and non-self
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naturally arising foxp3 expressing cd25 cd4 regulatory t cells in Immunological Tolerance to self and non self
Nature Immunology, 2005Co-Authors: Shimon SakaguchiAbstract:Naturally arising CD25+CD4+ regulatory T cells actively maintain Immunological self-Tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish transplantation Tolerance. They are therefore a good target for designing ways to induce or abrogate Immunological Tolerance to self and non-self antigens.
Louise C Kenny - One of the best experts on this subject based on the ideXlab platform.
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Immunological Tolerance pregnancy and preeclampsia the roles of semen microbes and the father
Frontiers in Medicine, 2018Co-Authors: Louise C Kenny, Douglas B KellAbstract:Although it is widely considered, in many cases, to involve two separable stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of pre-eclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its aetiology. However, apart from recognising, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focussed on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focussing on the Immunological Tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this Immunological Tolerance. As well as these benefits, however, semen is not sterile, microbial Tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus (and maybe the placenta) with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of pre-eclampsia. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination.
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Immunological Tolerance pregnancy and pre eclampsia the roles of semen microbes and the father
bioRxiv, 2017Co-Authors: Louise C Kenny, Douglas B KellAbstract:Abstract Although it is widely recognised as involving two stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of pre-eclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its aetiology. However, apart from recognising, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focussed on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focussing on the Immunological Tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this Immunological Tolerance. As well as these benefits, however, semen is not sterile, microbial Tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of preeclampsia. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination. “In one of the last articles which he wrote, the late Professor F J Browne (1958) expressed the opinion that all the essential facts about pregnancy toxaemia are now available and that all that is required to solve the problem is to fit them together in the right order, like the pieces of a jigsaw puzzle” [1] “It appears astonishing how little attention has been given in reproductive medicine to the maternal immune system over the last few decades.” [2]
Douglas B Kell - One of the best experts on this subject based on the ideXlab platform.
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Immunological Tolerance pregnancy and preeclampsia the roles of semen microbes and the father
Frontiers in Medicine, 2018Co-Authors: Louise C Kenny, Douglas B KellAbstract:Although it is widely considered, in many cases, to involve two separable stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of pre-eclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its aetiology. However, apart from recognising, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focussed on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focussing on the Immunological Tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this Immunological Tolerance. As well as these benefits, however, semen is not sterile, microbial Tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus (and maybe the placenta) with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of pre-eclampsia. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination.
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Immunological Tolerance pregnancy and pre eclampsia the roles of semen microbes and the father
bioRxiv, 2017Co-Authors: Louise C Kenny, Douglas B KellAbstract:Abstract Although it is widely recognised as involving two stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of pre-eclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its aetiology. However, apart from recognising, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focussed on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focussing on the Immunological Tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this Immunological Tolerance. As well as these benefits, however, semen is not sterile, microbial Tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of preeclampsia. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination. “In one of the last articles which he wrote, the late Professor F J Browne (1958) expressed the opinion that all the essential facts about pregnancy toxaemia are now available and that all that is required to solve the problem is to fit them together in the right order, like the pieces of a jigsaw puzzle” [1] “It appears astonishing how little attention has been given in reproductive medicine to the maternal immune system over the last few decades.” [2]
Barton F Haynes - One of the best experts on this subject based on the ideXlab platform.
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hiv broadly neutralizing antibodies and Immunological Tolerance vac7p 988
Journal of Immunology, 2014Co-Authors: Guang Yang, Kevin Wiehe, Nathan I Nicely, Barton F Haynes, John R Mascola, Pamela J Bjorkman, Garnett KelsoeAbstract:It is generally thought that many human antibodies (Ab) that neutralize multiple clades of HIV-1 (bnAbs) are self-reactive. We previously identified kynureninase as the primary self-antigen recognized by 2F5, suggesting that generation of Ab to the 2F5 epitope of HIV-1 may be proscribed by immune Tolerance, a notion supported by impaired B-cell development in mice expressing the 2F5 VH and VL regions. However, there is a lack of quantitative and systemic assessment of polyreactivity among HIV bnAbs. In addition, it is unknown whether other classes of HIV-1 bnAbs and non-neutralizing antibodies are also influenced by Immunological Tolerance. Here, we used protein microarrays to assess bnAb binding to over 9,600 human proteins and compared bnAb binding profiles to HIV non-neutralizing antibodies. We found that bnAbs as a class are more autoreactive and more polyreactive than non-neutralizers. Interestingly, 4 of 7 CD4bs bnAbs screened from 2 distinct lineages (VRC01, VRC02, CH103 and CH106) bind human protein ubiquitin ligase E3A (UBE3A). We confirmed this crossreactivity in ELISA, and demonstrated that UBE3A competitively inhibits gp120 binding to VRC01. Our results demonstrate that HIV-1 bnAbs are significantly more polyreactive and self-reactive than non-neutralizers, which may subject them to Immunological Tolerance control in vivo. Our identification of UBE3A as a self-antigen of bnAbs provides a mechanism for the rarity and delayed development of certain CD4bs bnAbs.
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p04 26 Immunological Tolerance prevents the expression of a broadly reactive neutralizing hiv 1 antibody
Retrovirology, 2009Co-Authors: Laurent Verkoczy, Garnett Kelsoe, Marilyn Diaz, T Holl, Yingbin Ouyang, Hilary Boutonverville, S M Alam, Huaxin Liao, Barton F HaynesAbstract:Background Developing a safe and effective HIV-1 vaccine has been hampered by the inability to design immunogens that can induce antibodies capable of potently neutralizing diverse HIV-1 strains. Despite the recognition of conserved HIV-1 envelope (Env) regions by rare, broadly neutralizing antibodies, these regions fail to induce protective antibodies when used as immunogens or in the context of natural infections. Various hypotheses have been offered to explain the absence of an effective immune response to Env determinants, including the suppression of this response by Immunological Tolerance. This hypothesis arose from the observation that broadly neutralizing HIV1 antibodies can cross-react with self-antigens.
Gwendalyn J Randolph - One of the best experts on this subject based on the ideXlab platform.
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liver inflammation abrogates Immunological Tolerance induced by kupffer cells
Hepatology, 2015Co-Authors: Felix Heymann, Julia Peusquens, Isis Ludwigportugall, Marlene Kohlhepp, Can Ergen, Patricia Maria Niemietz, Christian Martin, Nico Van Rooijen, Jordi Ochando, Gwendalyn J RandolphAbstract:The liver is essential for inducing Immunological Tolerance toward harmless antigens to maintain immune system homeostasis. However, the precise cellular mechanisms of Tolerance induction against particle-bound antigens, the role of the local hepatic microenvironment, and implications for therapeutic targets in immune-mediated diseases are currently unclear. In order to elucidate cellular mechanisms of Tolerance induction in healthy and injured liver, we developed a novel in vivo system combining the systemic delivery of low-dose peptide antigens coupled to inert particles, Immunological readouts, and sophisticated intravital multiphoton microscopy-based imaging of liver in mice. We show that liver resident macrophages, Kupffer cells (KCs), but not hepatic monocyte-derived macrophages or dendritic cells (DCs), are the central cellular scavenger for circulating particle-associated antigens in homeostasis. KC-associated antigen presentation induces CD4 T-cell arrest, expansion of naturally occurring Foxp3+CD25+ interleukin-10-producing antigen-specific regulatory T cells (Tregs) and tolerogenic immunity. Particle-associated Tolerance induction in the liver protected mice from kidney inflammation in T-cell-mediated glomerulonephritis, indicating therapeutic potential of targeting KC for immune-mediated extrahepatic disorders. Liver inflammation in two independent experimental models of chronic liver injury and fibrosis abrogated Tolerance induction and led to an immunogenic reprogramming of antigen-specific CD4 T cells. In injured liver, infiltrating monocyte-derived macrophages largely augment the hepatic phagocyte compartment, resulting in antigen redistribution between myeloid cell populations and, simultaneously, KCs lose signature markers of their tolerogenic phenotype. Conclusions: Hepatic induction of tissue-protective Immunological Tolerance against particulate antigens is dependent on KCs as well as on a noninflamed liver microenvironment, thereby providing mechanistic explanations for the clinical observation of immune dysfunction and Tolerance break in patients with advanced liver diseases. (Hepatology 2015;62:279-291)
