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T cells generated in the absence of a thoracic thymus fail to establish homeostasis.

Abstract：

:Cervical thymus mimics the thoracic thymus in supporting T-cell development and exists in a subset of mice and humans. Importantly, it remains unknown whether the cervical thymus can generate T cells that are self-tolerant in the complete absence of signals from the thoracic thymus. Using a fetal liver reconstitution model in thoracic thymectomized RAG(-/-) mice, we found that T cells could be generated without contribution from the thoracic thymus. However, these mice had decreased T cells, increased proportions of effector memory T cells and Treg phenotype cells, increased serum IgG1/2b, and increased frequency of T cells expressing IFN-γ, IL-17 or IL-10. Half of the mice that received a thoracic thymectomy and fetal liver cells, unlike sham surgery controls, developed substantial morbidity with age. Disease was associated with lymphopenia-driven activation rather than inherent defects in the cervical thymus, as both thoracic and cervical thymocytes could generate disease in lymphopenic recipients. Administration of the homeostatic cytokine IL-7 caused a rapid, transient increase in T-cell numbers and reduced the time to disease onset. Together the data suggests that the cervical thymus can function in the complete absence of the thoracic thymus; however, the T cells generated do not establish homeostasis.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Smolarchuk C,Zhu LF,Chan WF,Anderson CC

doi

10.1002/eji.201343846

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

2263-73

issue

8

eissn

0014-2980

issn

1521-4141

journal_volume

44

pub_type

杂志文章

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