Lymphotoxin β receptor controls T cell progenitor entry to the thymus

Beth Lucas, Kieran D. James, Emilie J. Cosway, Sonia M. Parnell, Alexei V Tumanov, Carl F. Ware, William E. Jenkinson, Graham Anderson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 b 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 LTbR 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. The Journal of Immunology, 2016, 197: 2665-2672.

Original languageEnglish (US)
Pages (from-to)2665-2672
Number of pages8
JournalJournal of Immunology
Volume197
Issue number7
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

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Lymphotoxin-alpha
T-Cell Antigen Receptor
Thymus Gland
T-Lymphocytes
Bone Marrow
Transplants
Stromal Cells
Allergy and Immunology
Bone Marrow Transplantation
Chemokines
Regeneration
Cell Count
Transplantation

ASJC Scopus subject areas

  • Immunology

Cite this

Lucas, B., James, K. D., Cosway, E. J., Parnell, S. M., Tumanov, A. V., Ware, C. F., ... Anderson, G. (2016). Lymphotoxin β receptor controls T cell progenitor entry to the thymus. Journal of Immunology, 197(7), 2665-2672. https://doi.org/10.4049/jimmunol.1601189

Lymphotoxin β receptor controls T cell progenitor entry to the thymus. / Lucas, Beth; James, Kieran D.; Cosway, Emilie J.; Parnell, Sonia M.; Tumanov, Alexei V; Ware, Carl F.; Jenkinson, William E.; Anderson, Graham.

In: Journal of Immunology, Vol. 197, No. 7, 01.10.2016, p. 2665-2672.

Research output: Contribution to journalArticle

Lucas, B, James, KD, Cosway, EJ, Parnell, SM, Tumanov, AV, Ware, CF, Jenkinson, WE & Anderson, G 2016, 'Lymphotoxin β receptor controls T cell progenitor entry to the thymus', Journal of Immunology, vol. 197, no. 7, pp. 2665-2672. https://doi.org/10.4049/jimmunol.1601189
Lucas, Beth ; James, Kieran D. ; Cosway, Emilie J. ; Parnell, Sonia M. ; Tumanov, Alexei V ; Ware, Carl F. ; Jenkinson, William E. ; Anderson, Graham. / Lymphotoxin β receptor controls T cell progenitor entry to the thymus. In: Journal of Immunology. 2016 ; Vol. 197, No. 7. pp. 2665-2672.
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