Evidence for a stepwise program of extrathymic T cell development within the human tonsil. J Clin Invest 2012 Apr;122(4):1403-15
Date
03/02/2012Pubmed ID
22378041Pubmed Central ID
PMC3314444DOI
10.1172/JCI46125Scopus ID
2-s2.0-84858793590 (requires institutional sign-in at Scopus site) 71 CitationsAbstract
The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34⁺CD38dimLin⁻ cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34⁺CD38brightLin⁻ cells; (c) CD34⁺CD1a⁺CD11c⁻ cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34⁻CD1a⁺CD3⁻CD11c⁻ cells, which resemble CD4⁺CD8⁺ double-positive T cells in the thymus; and (e) CD34⁻CD1a⁺CD3⁺CD11c⁻ cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT⁺ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre-T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development.
Author List
McClory S, Hughes T, Freud AG, Briercheck EL, Martin C, Trimboli AJ, Yu J, Zhang X, Leone G, Nuovo G, Caligiuri MAAuthors
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of WisconsinAnthony J. Trimboli PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antigens, CDAntigens, Differentiation, T-Lymphocyte
Cell Lineage
Hematopoietic Stem Cells
Homeodomain Proteins
Humans
Immunophenotyping
Killer Cells, Natural
Lymphopoiesis
Membrane Glycoproteins
Organ Specificity
Palatine Tonsil
Receptors, Antigen, T-Cell, alpha-beta
Stem Cell Niche
T-Lymphocyte Subsets
Thymus Gland
