α β and γ δ T cells can share a late common precursor

Dudley, Erastus C.; Girardi, Michael; Owen, Michael John; Hayday, Adrian

doi:10.1016/s0960-9822(95)00131-x

Cited by 128 publications

(118 citation statements)

References 45 publications

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“…In the first situation, it is predicted that the resulting DP cells carry in-frame TCR␦ and TCR␥ rearrangements despite the fact that they may not express these products as a possible consequence of their commitment to the ␣␤ lineage. Such cells would thus differ from DP cells of normal mice in which in-frame TCR␦ and TCR␥ joints appear to be counterselected (17,30). Conversely, in the second situation, rearrangements at the TCR␦ and TCR␥ loci would at least be expected to not be enriched for in-frame junctions.…”

Section: Tcr ␦ and ␥ Gene Rearrangements In E␤ ϫ/ϫ Dp ␥␦ ϩ And ␥␦ ϫ Tmentioning

confidence: 94%

“…Diverse TCR␦ and TCR␥ gene rearrangements were studied by PCR-RFLP, according to published protocols (11,30). Briefly, genomic DNA from sorted thymocytes was PCR-amplified using appropriate pairs of TCR␦ and TCR␥ primers as follows: V␦4-or V␦5-J␦1, 5Ј-CCATCGAT GGCCGCTTCTCTGTGAACTTCC-3Ј or 5Ј-CCATCGATGGCAGATC CTTCCAGTTCATCC-3Ј and 5Ј-CAGTCACTTGGGTTCCTTGTCC-3Ј; V␥2-J␥2, 5Ј-CCATCGATGGTACCGGCAAAAAACAAATC-3Ј and 5Ј-TGAATTCCTTCTGCAAATACCTTG-3Ј; and V␥4-J␥1, 5Ј-CCATCG ATGGTGTCCTTGCAACCCCTACCC-3Ј and 5Ј-TGAATTCCTTCTGC AAATACCTTG-3Ј.…”

Section: Pcr-rflpmentioning

confidence: 99%

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T Cell Development in TCRβ Enhancer-Deleted Mice: Implications for αβ T Cell Lineage Commitment and Differentiation

Leduc

Hempel

Mathieu

et al. 2000

The Journal of Immunology

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T cell differentiation in the mouse thymus is an intricate, highly coordinated process that requires the assembly of TCR complexes from individual components, including those produced by the precisely timed V(D)J recombination of TCR genes. Mice carrying a homozygous deletion of the TCRβ transcriptional enhancer (Eβ) demonstrate an inhibition of V(D)J recombination at the targeted TCRβ locus and a block in αβ T cell differentiation. In this study, we have characterized the T cell developmental defects resulting from the Eβ−/− mutation, in light of previously reported results of the analyses of TCRβ-deficient (TCRβ−/−) mice. Similar to the latter mice, production of TCRβ-chains is abolished in the Eβ−/− animals, and under these conditions differentiation into cell-surface TCR−, CD4+CD8+ double positive (DP) thymocytes depends essentially on the cell-autonomous expression of TCRδ-chains and, most likely, TCRγ-chains. However, contrary to previous reports using TCRβ−/− mice, a minor population of TCR γδ+ DP thymocytes was found within the Eβ−/− thymi, which differ in terms of T cell-specific gene expression and V(D)J recombinase activity, from the majority of TCR−, αβ lineage-committed DP thymocytes. We discuss these data with respect to the functional role of Eβ in driving αβ T cell differentiation and the mechanism of αβ T lineage commitment.

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Section: Tcr ␦ and ␥ Gene Rearrangements In E␤ ϫ/ϫ Dp ␥␦ ϩ And ␥␦ ϫ Tmentioning

confidence: 94%

Section: Pcr-rflpmentioning

confidence: 99%

T Cell Development in TCRβ Enhancer-Deleted Mice: Implications for αβ T Cell Lineage Commitment and Differentiation

Leduc

Hempel

Mathieu

et al. 2000

The Journal of Immunology

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Section: Introductionmentioning

confidence: 99%

“…Most preTCRs expressing DN3 will differentiate into the a/b T-cell lineage. However, a small proportion might still give rise to g/d T cells as suggested by the finding that about 20% of g/d T cells contain a TCR-b chain capable of forming a preTCR [21][22][23][24]. The vast majority of DN3 cells that express a TCR-b polypeptide will undergo a preTCR-mediated proliferative expansion [18][19][20] and will differentiate into DN4 cells.…”

mentioning

confidence: 99%

The preTCR‐dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL‐7 signaling

et al. 2011

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The requirement for Notch signaling during T-cell development has been extensively studied. Nevertheless, the developmental stage at which it is required and whether additional signaling pathways are needed are still poorly understood. By using a stromalcell-free culture system, we show that sorted double-negative 3 (DN3) thymocytes only require a Delta-like-4-induced Notch signal to differentiate into double-positive (DP) cells. This differentiation process is preTCR-a dependent. DN3 cells undergo 4-5 proliferation cycles, and the addition of the chemokine CXCL12 improves proliferation. IL-7 blocks the differentiation of DN3 cells to DP cells but not the Notch-induced proliferation of cultured DN3 cells. The impaired differentiation correlates with an inhibition of Rag-2 upregulation. Overall, the in vitro stromal-cell-free culture system presented here also provides a powerful and unique tool for studying the mechanisms involved in the positive and negative selection of T cells.Key words: Delta-like 4 and preTCR . DN3 cells . Double-positive cells . Notch IntroductionTo maintain T lymphopoiesis, progenitor cells from the BM constantly seed the thymus. In transplantation settings, it has been shown that different progenitors can home to the thymus and generate T cells [1][2][3][4][5][6][7][8][9]. However, under physiological conditions the role of each of these progenitors is still unclear. It is generally believed that the so-called thymic seeding precursor (TSP) still has the capability of generating B cells, NK cells, DCs and other myeloid cells [2,5,6,10,11]. Upon receiving the Notch signal, the differentiation potential towards the B-cell lineage of the TSP is rapidly lost [2,10,11], whereas other lineage options are still maintained [2,5,6,10,11]. However, a recent study using an IL-7Ra reporter mouse indicated that the non-T-cell lineage differentiation of these progenitors is not, or only very rarely, occurring under physiologic conditions [12,13].Within the thymus, the earliest thymocytes are characterized by the absence of CD4 and CD8 expression and are therefore called double-negative (DN) cells. Based on the expression of CD25, CD44 and CD117, DN cells can be subdivided into four subpopulations. DN1 cells express high cell surface levels of CD44 and CD117, and are negative for CD25, whereas their DN2 progeny express all three markers [14][15][16]. In vitro, DN1 and DN2 cells still possess the capacity to differentiate into NK cells, DCs and other myeloid cells [5,6,11,17] suggesting that they are not yet restricted to the T-cell lineage. T-cell commitment is achieved at the DN3 stage. However, the mechanisms operating . It is at this stage of development that the rearrangement of the TCR-b chain locus is completed, and the cells are selected for a productive TCR-b chain rearrangement, also known as the b-selection checkpoint [18][19][20]. DN3 cells that have rearranged their TCR-b chain locus unproductively can either differentiate into g/d T cells or will otherwise undergo apoptosis. DN3 cells car...

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“…Cells that succeed in expressing TCRgd continue differentiating along this pathway, whereas cells that fail to do so die. Consistent with this interpretation is the recurrent (7,48,50,51), although not absolute (44), finding that a large fraction of TCRbchains present in gd cells from adult mice are functional, suggesting that their precursors were initially selected through the pre-TCR. Moreover, the presence of TCR-negative preapoptotic DN4 cells that have been b selected (52) is predicted by this interpretation.…”

Section: Discussionmentioning

confidence: 71%

Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

Pereira

Boucontet

Cumano

2012

The Journal of Immunology

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How T cell progenitors engage into the γδ or αβ T cell lineages is a matter of intense debate. In this study, we analyzed the differentiation potential of single thymocytes from wild-type and TCRγδ-transgenic mice at two sequential early developmental stages. Double-negative (DN) 3 progenitors from both wild-type and transgenic mice retain the capacity to engage into both pathways, indicating that full commitment is only completed after this stage. More importantly, DN2 and DN3 progenitors from TCRγδ transgenic mice have strong biases for opposite fates, indicating that developmentally regulated changes, other than the production of a functional TCR, altered their likelihood to become a γδ or an αβ T cell. Thus, unlike the differentiation in other hematopoietic lineages, T cell progenitors did not restrict, but rather switch their differentiation potential as they developed.

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α β and γ δ T cells can share a late common precursor

Cited by 128 publications

References 45 publications

T Cell Development in TCRβ Enhancer-Deleted Mice: Implications for αβ T Cell Lineage Commitment and Differentiation

T Cell Development in TCRβ Enhancer-Deleted Mice: Implications for αβ T Cell Lineage Commitment and Differentiation

The preTCR‐dependent DN3 to DP transition requires Notch signaling, is improved by CXCL12 signaling and is inhibited by IL‐7 signaling

Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

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