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The journal of immunology : official journal of the American Association of Immunologists v.197 no.7, 2016년, pp.2665 - 2672   SCI SCIE
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Lymphotoxin β Receptor Controls T Cell Progenitor Entry to the Thymus

Lucas, Beth (Medical Research Council Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom ) ; James, Kieran D. (Medical Research Council Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom ) ; Cosway, Emilie J. (Medical Research Council Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom ) ; Parnell, Sonia M. (Medical Research Council Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom ) ; Tumanov, Alexi V. (Trudeau Institute, Saranac Lake, NY 12983 ) ; Ware, Carl F. (and ) ; Jenkinson, William E. (Infectious and Inflammatory Diseases Research Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037 ) ; Anderson, Graham (Medical Research Council Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom ) ;
  • 초록  

    The recruitment of lymphoid progenitors to the thymus is essential to sustain T cell production throughout life. Importantly, it also limits T lineage regeneration following bone marrow transplantation, and so contributes to the secondary immunodeficiency that is caused by delayed immune reconstitution. Despite this significance, the mechanisms that control thymus colonization are poorly understood. In this study, we show that in both the steady-state and after bone marrow transplant, lymphotoxin β receptor (LTβR) controls entry of T cell progenitors to the thymus. We show that this requirement maps to thymic stroma, further underlining the key importance of this TNFR superfamily member in regulation of thymic microenvironments. Importantly, analysis of the requirement for LTβR in relationship to known regulators of thymus seeding suggests that it acts independently of its regulation of thymus-homing chemokines. Rather, we show that LTβR differentially regulates intrathymic expression of adhesion molecules known to play a role in T cell progenitor entry to the thymus. Finally, Ab-mediated in vivo LTβR stimulation following bone marrow transplant enhances initial thymus recovery and boosts donor-derived T cell numbers, which correlates with increased adhesion molecule expression by thymic stroma. Collectively, we reveal a novel link between LTβR and thymic stromal cells in thymus colonization, and highlight its potential as an immunotherapeutic target to boost T cell reconstitution after transplantation.


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