High levels of the onco-protein Gfi-1 accelerate T-cell proliferation and inhibit activation induced T-cell death in Jurkat T-cells

Karsunky, Holger; Mende, Ines; Schmidt, Thorsten; Möröy, Tarik

doi:10.1038/sj/onc/1205216

Cited by 13 publications

(17 citation statements)

References 21 publications

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“…Moreover, this study could not address why some transcripts induced in vitro in stimulated NK cells and T cells were not increased in ABMR or TCMR. For example, GFI1 was not strongly associated with ABMR or TCMR, possibly because GFI1 can auto‐repress its expression and may be only transiently induced by stimuli . TNFSF14, SEMA7A, and RGS16 may have uncharacterized patterns of expression which may explain their weak associations with ABMR and TCMR.…”

Section: Discussionmentioning

confidence: 98%

Mechanistic Sharing Between NK Cells in ABMR and Effector T Cells in TCMR

Parkes

Halloran

Hidalgo

2018

American Journal of Transplantation

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Human organ allograft rejection depends on effector lymphocytes: NK cells in antibody-mediated rejection (ABMR) and effector T cells in T cell-mediated rejection (TCMR). We hypothesized that NK cell CD16a stimulation and CD8 T cell TCR/CD3 stimulation represent highly similar effector systems, and should lead to shared molecular changes between ABMR and TCMR. We studied similarity between soluble proteins and the transcripts induced in CD16a stimulated NK cells and TCR/CD3-stimulated T cells in vitro. Of 30 soluble mediators tested, CD16a-activated NK cells and CD3/TCR activated T cells produced the same limited set of five mediators-CCL3, CCL4, CSF2, IFNG, and TNF-and failed to produce 25 others. Many transcripts increased in stimulated NK cells were also increased in CD3-stimulated CD8 T cells (FDR < 0.05), including IFNG, CSF2, CCL3, CCL4, and XCL1. We hypothesized that shared transcripts not produced by other cell types should be expressed both in ABMR and TCMR kidney transplant biopsies. CD160, XCL1, TNFRSF9, and IFNG were selective for TCR/CD3-activated T cells and CD16a-NK cells and all were strongly increased in ABMR and TCMR. The molecules such as CD160 and XCL1 shared between NK cells in ABMR and effector T cells in TCMR may hold insights into important rejection mechanisms.

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Section: Discussionmentioning

confidence: 98%

Mechanistic Sharing Between NK Cells in ABMR and Effector T Cells in TCMR

Parkes

Halloran

Hidalgo

2018

American Journal of Transplantation

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“…After antigenic activation, resting B cells undergo somatic hypermutation and CSR to be able to produce antigen‐specific IgG, IgA or IgE immunoglobulin molecules 17–29. CSR involves genetic recombination to place the newly rearranged variable region gene segments (VDJ segments) to the respective α, γ or ε constant region (CH genes) encoding sequences 32.…”

Section: Discussionmentioning

confidence: 99%

“…Splenic cells from mice were labeled with CFSE (Molecular Probes) as previously described 21. In brief, 10 7 cells/mL in HBSS were stained with CFSE (1 μM) and incubated for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…Gfi1 is not readily detected in mature T cells, but can be induced upon antigenic stimulation 20. Gfi1 can accelerate T‐cell proliferation 21 and inhibits activation‐induced cell death in T cells very likely by repressing mediators of apoptosis 21. In transgenic mice, a constitutional over expression of Gfi1 in T cells predisposes for the development of T‐cell lymphomas, albeit at a low rate and with a low incidence 22, 23.…”

Section: Introductionmentioning

confidence: 97%

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The zinc finger protein Gfi1 is implicated in the regulation of IgG2b production and the expression of Iγ2b germline transcripts

et al. 2008

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Gfi1 is a zinc finger transcription factor that is undetectable in B lymphocytes but its expression rises rapidly upon antigenic stimulation or treatment with lipopolysaccharide (LPS). Here we show that Gfi1(-/-) mice have higher serum levels of gamma isotype immunoglobulin than WT animals. When challenged with antigen, Gfi1(-/-) mice react with accelerated formation of PNA+/CD19+ germinal center B cells and an increased production of antigen-specific IgG2a and IgG2b. Moreover, Gfi1(-/-) B cells secrete more IgG2a and IgG2b than WT cells and produce higher levels of Igamma2b sterile germline transcripts when cultured with LPS. While the proliferative response to stimulation with anti-IgM antibodies and plasma cell differentiation was normal in Gfi1(-/-) B cells, we found that mRNA and protein levels of TGFbeta1 were significantly increased in the absence of Gfi1. TGFbeta1 has been shown to be essential for the regulation of IgG subclass production and was previously found to selectively stimulate IgG2b secretion. Our findings reveal a new function of Gfi1 in the control of IgG isotype production.

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“…GFI1 is described to be involved in T‐cell lymphomagenesis and T‐cell development. It is also expressed in granulocytes and activated macrophages outside the lymphoid system (Karsunky et al , 2002a), but is exclusively restricted to cells of the haematopoietic system. Recent reports show that GFI1B is essential for the development and differentiation of erythroid and megakaryocytic lineages.…”

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confidence: 99%

Growth factor‐independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate

et al. 2006

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SummaryGrowth factor-independent 1B (GFI1B) is a transcription factor essential for the development and differentiation of erythroid and megakaryocytic lineages. We evaluated the GFI1B expression in erythroleukaemia and megakaryocytic leukaemia, as well as in patients with other subtypes of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), myelodysplastic syndrome (MDS), severe aplastic anaemia (SAA), myelofibrosis with myeloid metaplasia (MMM) and in healthy volunteers. GFI1B expression was increased at least threefold in patients with erythroleukaemia (P < 0AE01 compared with controls) and megakaryocytic leukaemia (P < 0AE05) as well as in their corresponding leukaemic cell lines HEL, K562, CMK and M-07e. Patients with undifferentiated or monocytic AML, ALL, MMM, MDS and CML had no significantly altered GFI1B expression, whereas GFI1B expression was decreased 10-fold in patients with SAA (P < 0AE0001 compared with controls). Silencing GFI1B by transfection with small interfering RNA (siRNA) markedly reduced the proliferation rate in the leukaemic cell lines HEL, K562 and NB4 (P < 0AE01). Concomitantly, we observed a two-to threefold increase in the apoptosis rate in these cells after transfection with siRNA towards GFI1B. Our data indicate that GFI1B plays a major role in AML-M6 and AML-M7 and qualifies as a target for anti-leukaemic strategies in these malignancies.

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High levels of the onco-protein Gfi-1 accelerate T-cell proliferation and inhibit activation induced T-cell death in Jurkat T-cells

Cited by 13 publications

References 21 publications

Mechanistic Sharing Between NK Cells in ABMR and Effector T Cells in TCMR

Mechanistic Sharing Between NK Cells in ABMR and Effector T Cells in TCMR

The zinc finger protein Gfi1 is implicated in the regulation of IgG2b production and the expression of Iγ2b germline transcripts

Growth factor‐independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate

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