T cells generated in the absence of a thoracic thymus fail to establish homeostasis.
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.
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
Christa
C
Smolarchuk
Lin Fu
LF
Zhu
William F N
WF
Chan
Colin C
CC
Anderson
D000818:Animals; D006706:Homeostasis; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*; D013909:Thorax / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D007074:Immunoglobulin G; D020381:Interleukin-17; D015851:Interleukin-7; D016753:Interleukin-10; D007371:Interferon-gamma
Autoimmunity; Homeostasis; Lymphopenia; Regulatory T cells; Thymopoiesis