Unique subset of natural killer cells develops from progenitors in lymph node

Veinotte, Linnea Lora; Halim, Timotheus Y.F.; Takei, Fumio

doi:10.1182/blood-2007-04-087577

Cited by 26 publications

(41 citation statements)

References 24 publications

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“…Previous studies found at least 50% of thymic NK cells carried TCRg rearrangements (4,5), and these authors concluded that thymic NK cells derive from early T cell precursors that had undergone TCRg rearrangements. However, those analyses were made using in vitro-expanded NK cell cultures isolated from thymus, lymph nodes or spleen (4,5), and the possibility of a small number of contaminating mature T cells was not rigorously excluded.…”

Section: Thymic Nk Cells Do Not Express Rag2 and Do Not Rearrange Thementioning

confidence: 99%

“…It was previously reported that a large proportion of CD127 + and CD127 2 NK cells from thymus and lymph nodes carry TCRg rearrangements (4,5), suggesting that they are derived from CD4…”

Section: Thymic Nk Cells Do Not Express Rag2 and Do Not Rearrange Thementioning

confidence: 99%

“…For example, one study proposed that thymic NK cells actually represent NK-like gd T cells (3), although this is inconsistent with the fact that thymic NK cells develop independently of Rag2 (2). The Takei laboratory reported TCRg rearrangements in a large fraction of NK cells in the thymus and lymph nodes (4,5) and suggested that thymic NK cells might share a precursor stage with T cells and thus represent failed T cell precursors (4). In addition, recent data showed that the population of NK cell progenitor cells in the BM encompasses cells with not only NK potential but also T as well as NK/T bipotent precursor cells (6).…”

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confidence: 99%

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Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Ribeiro

Hasan

Wilson

et al. 2010

The Journal of Immunology

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Although NK cells in the mouse are thought to develop in the bone marrow, a small population of NK cells in the thymus has been shown to derive from a GATA3-dependent pathway. Characteristically, thymic NK cells express CD127 and few Ly49 molecules and lack CD11b. Because these NK cells develop in the thymus, the question of their relationship to the T cell lineage has been raised. Using several different mouse models, we find that unlike T cells, thymic NK cells are not the progeny of Rorc-expressing progenitors and do not express Rag2 or rearrange the TCRγ locus. We further demonstrate that thymic NK cells develop independently of the Notch signaling pathway, supporting the idea that thymic NK cells represent bona fide NK cells that can develop independently of all T cell precursors.

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Section: Thymic Nk Cells Do Not Express Rag2 and Do Not Rearrange Thementioning

confidence: 99%

“…It was previously reported that a large proportion of CD127 + and CD127 2 NK cells from thymus and lymph nodes carry TCRg rearrangements (4,5), suggesting that they are derived from CD4…”

Section: Thymic Nk Cells Do Not Express Rag2 and Do Not Rearrange Thementioning

confidence: 99%

mentioning

confidence: 99%

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Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Ribeiro

Hasan

Wilson

et al. 2010

The Journal of Immunology

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“…ECFP 1 Thy1 1 expressing cells identified in Lat Inv mice can be subdivided into two subpopulations: Thy1 dull and Thy1 high . While Thy1 dull population has the characteristic of previously described thymic lineage of NK cells [21,27], Thy1 high population represents previously unknown population of cell surface CD3 À but intracellular CD3 1 lymphocytes, expressing low levels of pTa, Rag 1 and Rag 2 transcripts. This population accumulates with age and contains high frequency of random, unselected, postnatal TCR-g and TCR-d rearrangements and no TCR-b rearrangements.…”

Section: Discussionmentioning

confidence: 85%

“…Yet, phenotypic changes accompanying both thymic and extrathymic processes are grossly similar [19]. Recently it has also been shown that T-cell or thymic NK-cell committed precursors may exit the thymus before reaching DN3 stage and complete their maturation in the gut or peripheral lymph nodes, respectively [20,21]. Here, we identify a novel population of Thy1 high lymphocytes, containing elevated frequencies of TCR-g and TCR- d but not TCR-b rearrangements and which accumulated with age in peripheral lymphoid organs of homozygous LAT-deficient enhanced cyan fluorescence protein (ECFP) reporter mice (Lat Inv/Inv ) but not in heterozygous Lat 1/Inv mice.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Thy1⁺ lymphocytes rearranging TCR‐γδ genes in LAT‐deficient mice

et al. 2009

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Linker for activation of T cells (LAT) is an adaptor molecule indispensable for development of ab and cd T lymphocytes. Surprisingly, using a new model of LAT-deficient mice we found that despite arrested thymic development, a discrete population of cells with active Lat promoter, expressing Thy1 molecules, accumulated in peripheral lymphoid organs of homozygous (Lat Inv/Inv ) mutant mice. By measuring frequencies of TCR gene rearrangements in conjunction with a panel of cell surface Ag, we dissected two subsets of these Thy1 1 cells. Thy1 dull cells expressed markers of NK lymphocytes and contained low frequency of TCR-c gene rearrangements without detectable TCR-d rearrangements. Thy1 high cells resembled immature CD44 1 CD25 1 thymocytes and contained high frequency of non-productive TCR-c and TCR-d rearrangements, indicating that cells displaying molecular signatures of commitment toward cd T-cell lineage can develop and populate lymphoid tissues of LAT-deficient mice. Phenotypically similar Thy1 high cells were also found in lymph nodes of lymphocyte-deficient (Rag2 À/À ) mice but not in T lymphocyte proficient, heterozygous Lat 1/Inv mice suggesting that Thy1 high cells of LAT-deficient mice identified in this study accumulate in peripheral lymphoid organs as a result of congenital lymphopenia.Key words: Extrathymic lymphopoiesis . LAT . Thymopoiesis . Thy1 . g/d T cells Supporting Information available online IntroductionLinker for activation of T cells (LAT) belongs to a family of transmembrane adaptor proteins involved in transduction of immunoreceptor-mediated signals [1,2].It is expressed in a number of hematopoietic cell lineages including T cells [3], pre-B cells [4], NK lymphocytes [5], megakaryocytes [6] and mast cells [7]. However, physiological roles of LAT adaptor in these cell lineages seem variable. In LAT knockout mice, NK lymphocytes, megakaryocytes and mast cells show seemingly normal development [8] with only discrete deficiencies of particular signaling pathways [5][6][7]. During B-cell maturation LAT deficiency causes a partial developmental block at the pre-B-cell stage [9,10]. In contrast, development of ab and gd T cells is entirely dependent on LAT adaptor, which is essential for signaling at the pre-TCR and ''TCR-gd quality control'' checkpoints [8,11]. Neither ab nor gd T cells have previously been found to develop and/or colonize the periphery of LAT knockout mice.In the thymus the incoming earliest CD4 À CD8 À double negative (DN) T-cell precursors progress through discrete 2596developmental stages, which may be characterized by cell surface expression of c-kit (CD117), CD25 and CD44 molecules and rearrangement status of g,. Transitions from the most immature and heterogeneous DN1 stage (c-kit high CD25 À CD44 1 ) through DN2 stage (c-kit int CD25 1 CD44 1 ) toward DN3 stage (c-kit low CD25 1 CD44 À ) are TCR independent, since only at DN3 stage most cells committed to T-cell lineages express TCR/CD3 complexes and undergo gd or b selection resulting in transition to DN4 (c-kit...

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B‐cell co‐receptor CD72 is expressed on NK cells and inhibits IFN‐γ production but not cytotoxicity

et al. 2009

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NK cells have two main functions, namely cell-mediated cytotoxicity and production of cytokines. Multiple inhibitory receptors that regulate NK-cell cytotoxicity have been characterized whereas little is known about receptors regulating cytokine production. Here we report that CD72, which is considered to be an important co-receptor regulating B-cell activation, is also expressed on mouse NK cells. NK cells expressing high levels of CD72, upon stimulation with IL-12 and IL-18 or target cells, produce significantly less IFN-c than those expressing low levels of CD72, whereas both subsets are equally cytotoxic. Ectopic expression of CD72 in the murine NK-cell line KY2 inhibits cytokine-induced IFN-c production, and the inhibitory effect is diminished by mutations in the inhibitory motifs in the intracellular domain or replacement of the extracellular domain of CD72. Thus, CD72 is an inhibitory receptor on NK cells regulating cytokine production.

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Unique subset of natural killer cells develops from progenitors in lymph node

Cited by 26 publications

References 24 publications

Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Peripheral Thy1⁺ lymphocytes rearranging TCR‐γδ genes in LAT‐deficient mice

B‐cell co‐receptor CD72 is expressed on NK cells and inhibits IFN‐γ production but not cytotoxicity

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Unique subset of natural killer cells develops from progenitors in lymph node

Cited by 26 publications

References 24 publications

Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Cutting Edge: Thymic NK Cells Develop Independently from T Cell Precursors

Peripheral Thy1+ lymphocytes rearranging TCR‐γδ genes in LAT‐deficient mice

B‐cell co‐receptor CD72 is expressed on NK cells and inhibits IFN‐γ production but not cytotoxicity

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Peripheral Thy1⁺ lymphocytes rearranging TCR‐γδ genes in LAT‐deficient mice