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B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21.
- Source :
-
International immunology [Int Immunol] 2014 Jul; Vol. 26 (7), pp. 383-95. Date of Electronic Publication: 2014 Feb 04. - Publication Year :
- 2014
-
Abstract
- CpG oligodeoxynucleotides (CpG) and IL-21 are two promising agents for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells. Here, we demonstrate that treatment of B-CLL cells with CpG and IL-21 results in the development of antigen-presenting cell (APC)-like cells with cytotoxic features. These properties eventually give rise to B-CLL cell apoptosis, independently of their cytogenetic phenotype, whereas normal B-cell survival is not negatively affected by CpG/IL-21. APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation. Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21. In conclusion, CpG/IL-21-stimulated B-CLL cells acquire features that are reminiscent of killer dendritic cells, and which result in enhanced immunogenicity, cytotoxicity and apoptosis. Our results provide novel insights into the aberrant immune state of B-CLL cells and may establish a basis for the development of an innovative cellular vaccination approach in B-CLL.<br /> (© The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Aged
Aged, 80 and over
Antigen-Presenting Cells immunology
Antigen-Presenting Cells pathology
Apoptosis drug effects
B-Lymphocytes immunology
B-Lymphocytes pathology
Chemokine CXCL10 genetics
Chemokine CXCL10 immunology
Cytotoxicity, Immunologic drug effects
Female
Gene Expression Regulation, Leukemic
Granzymes genetics
Granzymes immunology
Humans
Immunophenotyping
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Leukemia, Lymphocytic, Chronic, B-Cell pathology
Male
Middle Aged
Perforin genetics
Perforin immunology
Primary Cell Culture
Recombinant Proteins pharmacology
Signal Transduction
T-Box Domain Proteins genetics
T-Box Domain Proteins immunology
Antigen-Presenting Cells drug effects
B-Lymphocytes drug effects
Interleukins pharmacology
Leukemia, Lymphocytic, Chronic, B-Cell immunology
Lymphocyte Activation drug effects
Oligodeoxyribonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2377
- Volume :
- 26
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24497611
- Full Text :
- https://doi.org/10.1093/intimm/dxu001