Extrathymic Pathways of T-cell Differentiation in the Liver and Other Organs

Abo, Toru; Watanabe, Hirotaka; Iiai, Tsuneo; Kimura, Michio; Ohtsuka, Kazuo; Sato, Kazunari; Ogawa, Makoto; Hirahara, Hiroyuki; Hashimoto, Shigeo; Sekikawa, Hiroho; Seki, Shu

doi:10.3109/08830189409061717

Cited by 72 publications

(54 citation statements)

References 154 publications

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“…29 Because the liver contains pluripotent hematopoietic stem cells (which can give rise to all lineage leukocytes) even after birth, 30,31 and the activation and increase of liver MNC accompanied by the involution of the thymus is always observed in bacterial infections, malignancies, autoimmune diseases, and aging 13,32 (for review, see Abo 32 ), the liver can thus demonstrate extramedullary hematopoiesis under certain physiopathological states in the host. 13,[30][31][32] NK1 ϩ T cells are dependent on MHC class I-like molecules, CD1, for their development in the thymus and the liver, because CD1-deficient mice and ␤ 2 -microglobulindeficient mice (which lack both CD1 and MHC class I molecules) do not have these cells in the liver and thymus. [33][34][35][36][37][38] It is therefore unlikely that NK1 ϩ T cells (as well as NK cells) recognize bacterial superantigens with MHC class II molecules on monocytes/macrophages or B cells.…”

Section: Discussionmentioning

confidence: 99%

Activation of mouse liver natural killer cells and NK1.1+T cells by bacterial superantigen-primed Kupffer cells

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Activation of mouse liver natural killer cells and NK1.1+T cells by bacterial superantigen-primed Kupffer cells

et al. 1999

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“…The detection of RAG expression in four whole liver speci- [24]. Evidence of extrathymic T cell maturation has been well documented in t h e intestinal epithelium of both mice [6,71 and humans [18, 251.…”

Section: T Lymphocyte Differentiation In Human Livermentioning

confidence: 99%

RAG1, RAG2 and pre‐T cell receptor α chain expression by adult human hepatic T cells: evidence for extrathymic T cell maturation

et al. 1996

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Flow cytometric analysis of cell suspensions obtained from normal adult liver tissue at the time of transplantation revealed significant populations of T lymphocytes. These were examined for molecular evidence of local T cell maturation using reverse transcription-polymerase chain reaction to detect expression of recombination activation gene 1 (RAG1), RAG2 and pre-T cell receptor alpha chain (pTalpha), which occurs only in early thymocyte development. Four specimens of whole liver were positive for RAG1 and RAG2 expression, whereas peripheral blood mononuclear cells from the same individuals were negative. To localize RAG expression, immature (CD2+CD7+) and mature (CD45R0+) T cell subpopulations were isolated by magnetic separation from hepatic and peripheral blood mononuclear cell preparations. We detected the expression of RAG1, RAG2 and pre-TCRalpha in five specimens of hepatic CD2+CD7+ but not in CD45RO+ hepatic lymphocytes. Four out of six specimens of CD2+CD7+ cells from the peripheral blood were negative for RAG1 and RAG2 while all six specimens were positive for pTalpha expression. These results suggest that pre-T cells are trafficking from the bone marrow or the thymus to other tissues to continue differentiation and selection in the context of an appropriate cellular and molecular environment. The presence of immature populations of T cells in the adult liver and high levels of RAG expression suggests that the adult liver provides such an environment for extrathymic T cell maturation. These findings may have important implications for tolerance induction after liver transplantation and offer help in understanding the etiology of autoimmune liver disease.

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“…The paracrine influence of OM is sufficient to induce T cell development in the LNs: nontransgenic fetal liver-derived progenitors generate CD4 ϩ CD8 ϩ cells as well as mature T cells in the LNs of nontransgenic recipients, whereupon OM is supplied in a paracrine manner by coinjected OM-transgenic hemopoietic cells (31). The OM-dependent extrathymic pathway generates both CD4 ϩ and CD8 ϩ T cells, which are diverse in terms of V␤ usage and show a more rapid turnover rate (5-bromo-2Ј-deoxyuridine pulse-chase assays) than thymus-derived T lymphocytes in wild-type mice (31 (34).…”

Section: Thymic and Extrathymic T Cell Development Pathways Followmentioning

confidence: 99%

Thymic and Extrathymic T Cell Development Pathways Follow Different Rules

Terra

Labrecque

Perreault

2002

The Journal of Immunology

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Separation between primary and secondary lymphoid organs is a universal feature in jawed vertebrates. Strikingly, oncostatin M (OM)-transgenic mice present massive extrathymic T cell development, localized exclusively in the lymph nodes (LN). According to the prevailing paradigm, the thymus is the main source of T lymphocytes in gnathostomes mainly because thymic epithelial cells have a unique ability to support early steps in T cell development. It is therefore remarkable that productive T cell development occurs in the OM+ LN, despite the absence of epithelial cells. The present study shows that in the OM+ LN: 1) MHC class I expression strictly on hemopoietic cells is sufficient to support the development of a diversified repertoire of CD8 T cells; 2) the efficiency of positive selection of specific TCR-transgenic T cells is not the same as in the thymus; 3) negative selection is very effective, despite the lack of an organized thymic-like medulla. Furthermore, our data suggest that extrathymic T lymphocytes developing in the OM+ LN undergo extensive postselection expansion because they live in the microenvironment in which they were positively selected. This work illustrates how the division of labor between primary and secondary lymphoid organs influences the repertoire and homeostasis of T lymphocytes.

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Extrathymic Pathways of T-cell Differentiation in the Liver and Other Organs

Cited by 72 publications

References 154 publications

Activation of mouse liver natural killer cells and NK1.1+T cells by bacterial superantigen-primed Kupffer cells

Activation of mouse liver natural killer cells and NK1.1+T cells by bacterial superantigen-primed Kupffer cells

RAG1, RAG2 and pre‐T cell receptor α chain expression by adult human hepatic T cells: evidence for extrathymic T cell maturation

Thymic and Extrathymic T Cell Development Pathways Follow Different Rules

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