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 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.
Centre for Immune Regulation, Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
Audun
A
Os
Simone
S
Bürgler
Anna Parente
AP
Ribes
Ane
A
Funderud
Dong
D
Wang
Keith M
KM
Thompson
Geir E
GE
Tjønnfjord
Bjarne
B
Bogen
Ludvig A
LA
Munthe
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology*; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000276:immunology