Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells
There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory...
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doaj-e93e963acec147dbbab6bb8c9617a2732020-11-25T01:14:52ZengElsevierCell Reports2211-12472013-08-014356657710.1016/j.celrep.2013.07.011Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper CellsAudun Os0Simone Bürgler1Anna Parente Ribes2Ane Funderud3Dong Wang4Keith M. Thompson5Geir E. Tjønnfjord6Bjarne Bogen7Ludvig A. Munthe8Centre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayDepartment of Hematology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, NorwayCentre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory Th cells that were specific for endogenous CLL antigens. These Th cells activated autologous CLL cell proliferation in vitro and in human → mouse xenograft experiments. Moreover, CLL cells were efficient antigen-presenting cells that could endocytose and process complex proteins through antigen uptake pathways, including the B cell receptor. Activation of CLL cells by Th cells was contact and CD40L dependent. The results suggest that CLL is driven by ongoing immune responses related to Th cell–CLL cell interaction. We propose that Th cells support malignant B cells and that they could be targeted in the treatment of CLL. http://www.sciencedirect.com/science/article/pii/S2211124713003586 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Audun Os Simone Bürgler Anna Parente Ribes Ane Funderud Dong Wang Keith M. Thompson Geir E. Tjønnfjord Bjarne Bogen Ludvig A. Munthe |
spellingShingle |
Audun Os Simone Bürgler Anna Parente Ribes Ane Funderud Dong Wang Keith M. Thompson Geir E. Tjønnfjord Bjarne Bogen Ludvig A. Munthe Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells Cell Reports |
author_facet |
Audun Os Simone Bürgler Anna Parente Ribes Ane Funderud Dong Wang Keith M. Thompson Geir E. Tjønnfjord Bjarne Bogen Ludvig A. Munthe |
author_sort |
Audun Os |
title |
Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells |
title_short |
Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells |
title_full |
Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells |
title_fullStr |
Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells |
title_full_unstemmed |
Chronic Lymphocytic Leukemia Cells Are Activated and Proliferate in Response to Specific T Helper Cells |
title_sort |
chronic lymphocytic leukemia cells are activated and proliferate in response to specific t helper cells |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-08-01 |
description |
There is increasing interest in the chronic lymphocytic leukemia (CLL) microenvironment and the mechanisms that may promote CLL cell survival and proliferation. A role for T helper (Th) cells has been suggested, but current evidence is only circumstantial. Here we show that CLL patients had memory Th cells that were specific for endogenous CLL antigens. These Th cells activated autologous CLL cell proliferation in vitro and in human → mouse xenograft experiments. Moreover, CLL cells were efficient antigen-presenting cells that could endocytose and process complex proteins through antigen uptake pathways, including the B cell receptor. Activation of CLL cells by Th cells was contact and CD40L dependent. The results suggest that CLL is driven by ongoing immune responses related to Th cell–CLL cell interaction. We propose that Th cells support malignant B cells and that they could be targeted in the treatment of CLL.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713003586 |
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