Thymus

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Laura P. Hale - One of the best experts on this subject based on the ideXlab platform.

  • the role of the Thymus in immune reconstitution in aging bone marrow transplantation and hiv 1 infection
    Annual Review of Immunology, 2000
    Co-Authors: Barton F Haynes, M L Markert, Gregory D Sempowski, Dhavalkumar D Patel, Laura P. Hale
    Abstract:

    The human Thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human Thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the Thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal Thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal Thymus function that, taken together, support the notion that the human Thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.

  • Transplantation of Thymus Tissue in Complete DiGeorge Syndrome
    The New England journal of medicine, 1999
    Co-Authors: M. Louise Markert, Andreas Boeck, Laura P. Hale, Amy Kloster, Tanya M. Mclaughlin, Milena N. Batchvarova, Daniel C. Douek, Richard A. Koup, Donna D. Kostyu, Frances E. Ward
    Abstract:

    Background The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and Thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function. Methods We treated five infants (age, one to four months) with complete DiGeorge syndrome by transplantation of cultured postnatal Thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the Thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell–receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell–receptor genes. Results After the transplantation of Thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted Thymus in the s...

  • the human Thymus a chimeric organ comprised of central and peripheral lymphoid components
    Immunologic Research, 1998
    Co-Authors: Barton F Haynes, Laura P. Hale
    Abstract:

    Abstract The human Thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Although the Thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal Thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency Virus (HIV) leads to severe loss of CD4+ T cells, has come the need to understand the role of the human Thymus in reconstitution of the immune system in adults. During a recent study of the Thymus in HIV infection, we observed many CD8+ T cells in AIDS Thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8+ effector T cells were predominantly located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the Thymus in HIV-1 infection, and discusses the work of others that, taken together, suggest that the Thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout normal life during the process of Thymus involution. Thus, the human Thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-1 infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.

Barton F Haynes - One of the best experts on this subject based on the ideXlab platform.

  • the role of the Thymus in immune reconstitution in aging bone marrow transplantation and hiv 1 infection
    Annual Review of Immunology, 2000
    Co-Authors: Barton F Haynes, M L Markert, Gregory D Sempowski, Dhavalkumar D Patel, Laura P. Hale
    Abstract:

    The human Thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human Thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the Thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal Thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal Thymus function that, taken together, support the notion that the human Thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.

  • the human Thymus a chimeric organ comprised of central and peripheral lymphoid components
    Immunologic Research, 1998
    Co-Authors: Barton F Haynes, Laura P. Hale
    Abstract:

    Abstract The human Thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Although the Thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal Thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency Virus (HIV) leads to severe loss of CD4+ T cells, has come the need to understand the role of the human Thymus in reconstitution of the immune system in adults. During a recent study of the Thymus in HIV infection, we observed many CD8+ T cells in AIDS Thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8+ effector T cells were predominantly located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the Thymus in HIV-1 infection, and discusses the work of others that, taken together, suggest that the Thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout normal life during the process of Thymus involution. Thus, the human Thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-1 infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.

Maria J Jordan - One of the best experts on this subject based on the ideXlab platform.

  • antimicrobial activity and chemical composition of Thymus vulgaris Thymus zygis and Thymus hyemalis essential oils
    Food Control, 2008
    Co-Authors: Maria C Rota, Antonio Herrera, Rosa M Martinez, Jose A Sotomayor, Maria J Jordan
    Abstract:

    Abstract The present study describes the volatile profile and antimicrobial activity of Thymus vulgaris (thymol chemotype), Thymus zygis subsp. gracilis (thymol and two linalool chemotypes) and Thymus hyemalis Lange (thymol, thymol/linalool and carvacrol chemotypes) essential oils extracted from seven plants cultivated in Murcia (Spain). Antimicrobial activities of the oils were evaluated for control of growth and survival of 10 pathogenic microorganisms. Gas chromatography–mass spectrometry analysis allowed for the identification of between 42 and 51 compounds as main volatile constituents of each essential oil analyzed. Results presented here may suggest that the essential oils from T. hyemalis (thymol) followed by T. hyemalis (carvacrol), T. zygis (thymol) and T. vulgaris possesses antimicrobial properties, and are a potential source of antimicrobial ingredients for the food industry.

Hans Reimer Rodewald - One of the best experts on this subject based on the ideXlab platform.

  • Thymus autonomous t cell development in the absence of progenitor import
    Journal of Experimental Medicine, 2012
    Co-Authors: Vera C Martins, Eliana Ruggiero, Susan M Schlenner, Vikas Madan, Manfred Schmidt, Pamela J Fink, Christof Von Kalle, Hans Reimer Rodewald
    Abstract:

    Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the Thymus lacks progenitors with self-renewal capacity is based on Thymus transplantation experiments in which host-derived thymocytes replaced Thymus-resident cells within 4 wk. Thymus grafting into T cell–deficient mice resulted in a wave of T cell export from the Thymus, followed by colonization of the Thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2−/−γc−/−KitW/Wv mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type Thymus grafts, we noticed Thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from Thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived Thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2−/−γc−/−KitW/Wv hosts, γc-mediated signals alone played a key role in the competition between Thymus-resident and bone marrow–derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the Thymus.

  • neural crest origin of perivascular mesenchyme in the adult Thymus
    Journal of Immunology, 2008
    Co-Authors: Susanna M Muller, Claus C Stolt, Grzegorz Terszowski, Carmen Blum, Takashi Amagai, Nicoletta Kessaris, Palma Iannarelli, William D Richardson, Michael Wegner, Hans Reimer Rodewald
    Abstract:

    The endodermal epithelial Thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-NC interaction is crucial for Thymus development, but it is not known how NC supports Thymus development or whether NC cells or their progeny make any significant contribution to the adult Thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate Thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-independent mesenchymal cell population. These mesenchymal cells expressed vascular endothelial growth factor-A, and contributed to Thymus vascularization. These data suggested a physical or functional association with thymic blood vessels, but the origin, location in the Thymus, and function of these stromal cells remained unknown. Using a transgenic mouse expressing Cre recombinase in premigratory NC (Sox10-Cre), we have now fate-mapped the majority of these adult mesenchymal cells to a NC origin. NC-derived cells represent tightly vessel-associated pericytes that are sandwiched between endothelium and epithelium along the entire Thymus vasculature. The ontogenetic, phenotypic, and positional definition of this distinct perivascular mesenchymal compartment provides a cellular basis for the role of NC in Thymus development and possibly maintenance, and might be useful to address properties of the endothelial-epithelial barrier in the adult Thymus.

Jerome A Zack - One of the best experts on this subject based on the ideXlab platform.

  • the scid hu mouse as a model for hiv 1 infection
    Nature, 1993
    Co-Authors: Grace M Aldrovandi, Gerold Feuer, Lianying Gao, Beth D Jamieson, Marlene Kristeva, Irvin S Y Chen, Jerome A Zack
    Abstract:

    DURING normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the Thymus1. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the Thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women2–5. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse6 as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect7,8. The model is constructed by implanting human fetal liver and Thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.