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Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development

  • Immunology at Mount Sinai
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Abstract

During thymocyte development bone marrow-derived precursors in the thymus undergo a series of differentiation steps to produce self-tolerant, mature T lymphocytes. The thymus contains two functionally distinct anatomical compartments, consisting of a centrally located medulla surrounded by the thymic cortex. These compartments in turn are comprised of two major cellular components: (1) the T lymphoid compartment of developing thymocytes and (2) the thymic stroma consisting mainly of thymic epithelial cells (TECs). These epithelial cells are further separated into cortical and medullary TECs (cTECs and mTECs) based on their localization within the thymic cortex or medulla respectively. Reciprocal interactions between thymocytes and epithelial cells are required for the development of both cellular components into a functional thymic organ. Thymocytes provide trophic factors for the development of a complex three-dimensional epithelial cell network, while epithelial cells regulate T cell development through expression and presentation of self-antigens on major histocompatibility molecules. Our work focuses on how thymic epithelial cells regulate T cell development and function and on elucidating the mechanisms of thymic epithelial cell differentiation. Here we review current knowledge and provide our own insight into the development, differentiation and antigen presenting properties of TECs. We focus specifically on how mTECs regulate T cell repertoire selection and central tolerance.

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Acknowledgments

The authors would like to thank Dr. Yongwon Choi (University of Pennsylvania) for his kind gift of recombinant RANKL. K.A was supported by the National Institute of Allergy and Infectious Disease (NIAID) grants RO1 AI49387-01; R56 AI049387-05; R01 AI068963-01. N.M.D was supported by Columbia University’s Immunology Program training grant T32 AI007525-10 and by NIAID grant R01 AI068963-01.

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  1. Division of Clinical Immunology, Department of Medicine, The Immunology Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1089, New York, NY, 10029, USA

    Konstantina Alexandropoulos

  2. Center for Translational Immunology, Columbia University Medical Center, 630 West 168th Street BB1511, New York, NY, 10032, USA

    Nichole M. Danzl

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  1. Konstantina Alexandropoulos
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Correspondence to Konstantina Alexandropoulos.

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Alexandropoulos, K., Danzl, N.M. Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development. Immunol Res 54, 177–190 (2012). https://doi.org/10.1007/s12026-012-8301-y

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