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Thymic Education of Human T Cells and Regulatory T Cell Development in Humanized Mice

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Abstract

The thymus is an organ that generates and educates T cells, supplying T subsets that ensure adaptive immunity and self-tolerance. Intrathymic positive selection of T cells with further post-thymic maturation and signaling provided by peripheral antigen-presenting cells (APCs) sustains a functional and regulated T cell pool. Intrathymic negative selection and generation of natural regulatory T cells (Tregs) in the thymus are essential to contain T cell autoimmunity. Humanized mouse models provide a unique opportunity to investigate these processes and their underlying mechanisms. Humanized mice can be generated by injecting human hematopoietic stem cells, with or without cotransplantation of fetal thymic tissue, to immunodeficient mice. Human thymopoiesis and T cell development in the former and latter models occur in the recipient mouse thymus and human thymic grafts, respectively. In this chapter, we summarize information on human T cell development, post-thymic interactions between T cells and APCs, as well as mechanisms maintaining tolerance that has been learned from these humanized mouse models.

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Acknowledgments

We thank Shavree Washington for assistance with the manuscript. The work of the authors discussed in this chapter was supported by the following NIH grants: RO1AI084074 (to Sykes), RC1HL100117 and R01 AI064569 (to Yang) and P01AI045897 (to Sykes and Yang) and JDRF grant 1-2007-1057 (to Sykes).

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Authors and Affiliations

  1. Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Hao Wei Li & Yong-Guang Yang

  2. First Hospital of Jilin University, Changchun, China

    Yong-Guang Yang

  3. Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, 650 West 168th Street, Black Building 1512, 10032, New York, NY, USA

    Dr. Megan Sykes MD

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  1. Hao Wei Li
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  2. Yong-Guang Yang
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  3. Dr. Megan Sykes MD
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Correspondence to Megan Sykes MD .

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Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

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Li, H., Yang, YG., Sykes, M. (2014). Thymic Education of Human T Cells and Regulatory T Cell Development in Humanized Mice. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_11

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