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  EOMES and IL-10 regulate antitumor activity of T regulatory type 1 CD4+ T cells in chronic lymphocytic leukemia

Roessner, P. M., Cid, L. L., Lupar, E., Roider, T., Bordas, M., Schifflers, C., et al. (2021). EOMES and IL-10 regulate antitumor activity of T regulatory type 1 CD4+ T cells in chronic lymphocytic leukemia. Leukemia: the Journal of Normal and Malignant Hemopoiese; Official Journal of the Leukemia Research Fund U.K., 35, 2311-2324. doi:10.1038/s41375-021-01136-1.

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 Creators:
Roessner, Philipp M1, Author
Cid, Laura Llaó1, Author
Lupar, Ekaterina2, Author
Roider, Tobias1, Author
Bordas, Marie1, Author
Schifflers, Christoph1, Author
Arseni, Lavinia1, Author
Gaupel, Ann-Christin1, Author
Kilpert, Fabian3, Author
Krötschel, Marit4, Author           
Arnold, Sebastian J1, Author
Sellner, Leopold1, Author
Colomer, Dolors1, Author
Stilgenbauer, Stephan1, Author
Dietrich, Sascha1, Author
Lichter, Peter1, Author
Izcue, Ana2, Author           
Seiffert, Martina1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              
3Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_persistent22              
4Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Abstract: The transcription factor eomesodermin (EOMES) promotes interleukin (IL)-10 expression in CD4+ T cells, which has been linked to immunosuppressive and cytotoxic activities. We detected cytotoxic, programmed cell death protein-1 (PD-1) and EOMES co-expressing CD4+ T cells in lymph nodes (LNs) of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell lymphoma. Transcriptome and flow cytometry analyses revealed that EOMES does not only drive IL-10 expression, but rather controls a unique transcriptional signature in CD4+ T cells, that is enriched in genes typical for T regulatory type 1 (TR1) cells. The TR1 cell identity of these CD4+ T cells was supported by their expression of interferon gamma and IL-10, as well as inhibitory receptors including PD-1. TR1 cells with cytotoxic capacity accumulate also in Eµ-TCL1 mice that develop CLL-like disease. Whereas wild-type CD4+ T cells control TCL1 leukemia development after adoptive transfer in leukopenic Rag2-/- mice, EOMES-deficient CD4+ T cells failed to do so. We further show that TR1 cell-mediated control of TCL1 leukemia requires IL-10 receptor (IL-10R) signaling, as Il10rb-deficient CD4+ T cells showed impaired antileukemia activity. Altogether, our data demonstrate that EOMES is indispensable for the development of IL-10-expressing, cytotoxic TR1 cells, which accumulate in LNs of CLL patients and control TCL1 leukemia in mice in an IL-10R-dependent manner.

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Language(s): eng - English
 Dates: 2021-02-01
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41375-021-01136-1
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Title: Leukemia : the Journal of Normal and Malignant Hemopoiese ; Official Journal of the Leukemia Research Fund U.K.
  Other : Leukemia (Online-Ausg.)
Source Genre: Journal
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Publ. Info: Basingstoke : Nature Publ. Group
Pages: - Volume / Issue: 35 Sequence Number: - Start / End Page: 2311 - 2324 Identifier: ISSN: 1476-5551
ISSN: 0887-6924
CoNE: https://pure.mpg.de/cone/journals/resource/954925554401