Interleukin 7 induces tcr gene rearrangement in adult marrow-resident murine precursor T cells

Soloff, Rachel; Wang, Tong-Gang; Dempsey, Deborah; Jennings, Stephen R.; Wolcott, R. Michael; Chervenak, Robert

doi:10.1016/s0161-5890(97)00051-5

Cited by 11 publications

(3 citation statements)

References 37 publications

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“…De novo generation of TCR-γδ IELs in iFABP-IL7 mice indicated that all IL-7–dependent steps of T cell development occurred within the intestine, including commitment to the TCR-γδ cell lineage. It is agreed that IL-7R signaling influences TCR-γ gene rearrangement 52535455 or expression of TCRVγ genes 56575859606162. Since signaling through IL-7R promotes TCR-γ gene rearrangement and/or transcription, then IL-7 produced within the intestine provided the stimulus to initiate extrathymic development of TCR-γδ cells.…”

Section: Discussionmentioning

confidence: 99%

Enterocyte Expression of Interleukin 7 Induces Development of γδ T Cells and Peyer's Patches

Laky

Lefrançois

Lingenheld

et al. 2000

The Journal of Experimental Medicine

136

106

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The intestinal mucosa is suggested to support extrathymic T cell development, particularly for T cell receptor (TCR)-γδ intraepithelial lymphocytes (IELs). TCR-γδ cell development requires interleukin (IL)-7; IL-7−/− or IL-7 receptor−/− mice lack TCR-γδ cells. Using the intestinal fatty acid binding protein (iFABP) promoter, we reinstated expression of IL-7 to mature enterocytes of IL-7−/− mice (iFABP-IL7). In iFABP-IL7 mice, TCR-γδ IELs were restored, as were cryptopatches and Peyer's patches. TCR-γδ cells remained absent from all other tissues. Likewise, T cell development in thymus and B cell maturation in the bone marrow and spleen retained the IL-7−/− phenotype. Thus, IL-7 expression by enterocytes was sufficient for extrathymic development of TCR-γδ cells in situ within the intestinal epithelium and was crucial for organization of mucosal lymphoid tissue.

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Section: Discussionmentioning

confidence: 99%

Enterocyte Expression of Interleukin 7 Induces Development of γδ T Cells and Peyer's Patches

Laky

Lefrançois

Lingenheld

et al. 2000

The Journal of Experimental Medicine

136

106

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“…Addition of IL-7 to cultures of E14 fetal liver cells, adult BM T cell precursors, or mature TCR␣␤ HSA low CD4 ϩ thymocytes yields in-frame, junctionally diverse TCRV␥1.2, TCRV␥2, or TCRV␥4 transcripts (8,(17)(18)(19)(20). In all instances, TCR␥ mRNAs are not found in cells cultured without IL-7.…”

mentioning

confidence: 96%

Distinct Requirements for IL-7 in Development of TCRγδ Cells During Fetal and Adult Life

Laky

Lewis

Tigelaar

et al. 2003

The Journal of Immunology

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TCRγδ-transgenic IL-7−/− mice were generated to determine whether T cells containing productively rearranged TCRγδ genes have additional requirements for IL-7 within the thymus or peripheral lymphoid tissues. Differences in developmental requirements for IL-7 by TCRγδ cells were noted and were linked to derivation from fetal- vs adult-type precursors in the thymus. Although TCRγδ cells are absent from IL-7−/− mice, TCRγδ cells were restored to the thymus and periphery by expression of TCRγδ transgenes. Endogenous TCRγ chains were expressed by IL-7+/− but not IL-7−/− TCRγδ-transgenic mice, providing direct support for findings that IL-7 is necessary for rearrangement and expression of TCRγ genes. The number of TCRγδ thymocytes was 10-fold reduced in TCRγδ-transgenic IL-7−/− embryos; however, adult TCRγδ-transgenic IL-7−/− or IL-7+/− mice had similar numbers of fetal thymus-derived TCRγδ cells in their skin. Thus, fetal TCRγδ cells required IL-7 for TCR rearrangement, but not for proliferation or survival in the periphery. In contrast, the numbers of TCRγδ cells in other tissues of TCRγδ-transgenic IL-7−/− mice were not completely restored. Moreover, coincident with the transition from the first to second wave of T cell precursors maturing in neonatal thymus, thymus cellularity of TCRγδ-transgenic IL-7−/− mice dropped significantly. These data indicated that in addition to TCRVγ gene rearrangement, TCRγδ cells differentiating from late fetal liver or adult bone marrow precursors have additional requirements for IL-7. BrdU incorporation studies indicated that although IL-7 was not required for TCRγδ cell proliferation, it was required to prolong the life span of mature TCRγδ cells.

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“…What determines the molecular changes that modulate accessibility for the VDJ recombinase to its chromatin templates? The mechanism responsible for chromatin modification was studied in a mouse model in which induction of VDJ recombination depends on an external signal 8–12. The cytokine interleukin‐7 (IL‐ 7) is crucial for lymphoid development 13,14.…”

Section: Control Of Vdj Recombination By Chromatin Accessibilitymentioning

confidence: 99%

Epigenetic Control during Lymphoid Development and Immune Responses

Muegge

Young

Ruscetti

et al. 2003

Annals of the New York Academy of Sciences

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Methylation of cytosines controls a number of biologic processes such as imprinting and X chromosomal inactivation. DNA hypermethylation is closely associated with transcriptional silencing, while DNA hypomethylation is associated with transcriptional activation. Hypoacetylation of histones leads to compact chromatin with reduced accessibility to the transcriptional machinery. Methyl-CpG binding proteins can recruit corepressors and histone deacetylases; thus, the interplay between these epigenetic mechanisms regulates gene activation. Methylation has been implicated as an important mechanism during immune development, controlling VDJ recombination, lineage-specific expression of cell surface antigens, and transcriptional regulation of cytokine genes during immune responses. Aberrations in epigenetic machinery, either by genetic mutations or by somatic changes such as viral infections, are associated with early alterations in chronic diseases such as immunodeficiency and cancer.

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Interleukin 7 induces tcr gene rearrangement in adult marrow-resident murine precursor T cells

Cited by 11 publications

References 37 publications

Enterocyte Expression of Interleukin 7 Induces Development of γδ T Cells and Peyer's Patches

Enterocyte Expression of Interleukin 7 Induces Development of γδ T Cells and Peyer's Patches

Distinct Requirements for IL-7 in Development of TCRγδ Cells During Fetal and Adult Life

Epigenetic Control during Lymphoid Development and Immune Responses

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