Extrathymic pathways of T cell differentiation.
It is known that the liver is a major hematopoietic organ at fetal stages, but the hematopoiesis of this organ ceases at birth. However, the liver is still found to comprise c-kit+ stem cells and gives rise to extrathymic T cells, NK cells, and even granulocytes after birth. Extrathymic T cells generated in the liver of mice are identified as intermediate TCR (TCRint) cells, which include the NK1.1+TCRint (i.e. NKT cells) and NK1.1-TCRint subsets. Although extrathymic T cells are few in number during youth, they increase in number with advancing age. The number and function of extrathymic T cells are also elevated under conditions of stress, infections, malignancy, pregnancy, autoimmune diseases, chronic GVH diseases, etc. Under these conditions, the mainstream of T cell differentiation in the thymus, which produces conventional T cells, is inversely suppressed. Extrathymic T cells comprise self-reactive forbidden clones and mediate cytotoxicity against abnormal self-cells. Therefore, they might be beneficial for the elimination of such cells. However, over-activation of extrathymic T cells might be responsible for the onset of certain autoimmune diseases.
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Department of Immunology, Niigata University School of Medicine, Japan. immunol2@med.niigata-u.ac.jp
D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D006410:Hematopoiesis; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000166:cytology; D051379:Mice; D010802:Phylogeny; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D011948:Receptors, Antigen, T-Cell