Myeloid leukemia cells with a B7‐2+ subpopulation provoke Th‐cell responses and become immuno‐suppressive through the modulation of B7 ligands. Issue 3 (31st January 2013)
- Record Type:
- Journal Article
- Title:
- Myeloid leukemia cells with a B7‐2+ subpopulation provoke Th‐cell responses and become immuno‐suppressive through the modulation of B7 ligands. Issue 3 (31st January 2013)
- Main Title:
- Myeloid leukemia cells with a B7‐2+ subpopulation provoke Th‐cell responses and become immuno‐suppressive through the modulation of B7 ligands
- Authors:
- Dolen, Yusuf
Esendagli, Gunes - Abstract:
- <abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Expression of the B7 family molecules in acute myeloid leukemia (AML) has been demonstrated by independent clinical studies. Intriguingly, the expression of the most potent costimulatory molecules B7‐2 (CD86) and B7‐H2 (ICOS Ligand) on AML cells has been associated with poor prognosis and disease severity. Here, this phenomenon was modeled in vitro with the myeloid leukemia cell line HL‐60, which is capable of differentiating through the FAB M2/M3 and M4/M5 immunophenotypes. These derivatives of HL‐60 harbored a B7‐2<sup>+</sup> subpopulation and recapitulated the distribution of B7 ligands previously reported in primary AML cases. B7‐2<sup>+</sup> AML cells significantly contributed to T‐cell responses. This costimulatory activity enabled helper (Th)‐cell activation, proliferation, and production of Th1‐associated cytokines. Conversely, even a short‐term incubation with stimulated T cells resulted in upregulation of inhibitory B7‐H1 (PD‐L1) and B7‐DC (PD‐L2), and downregulation of stimulatory B7‐H2 molecules on leukemia cells. Purified from iHL‐60‐T‐cell co‐cultures, these myeloid leukemia cells severely suppressed Th‐cell responses specifically through the PD‐1 pathway. In conclusion, Th‐cell responses can be directly supported by B7‐2<sup>+</sup> leukemia subpopulations. However, this interaction can facilitate the acquisition of a suppressive character that may contribute to immune<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Expression of the B7 family molecules in acute myeloid leukemia (AML) has been demonstrated by independent clinical studies. Intriguingly, the expression of the most potent costimulatory molecules B7‐2 (CD86) and B7‐H2 (ICOS Ligand) on AML cells has been associated with poor prognosis and disease severity. Here, this phenomenon was modeled in vitro with the myeloid leukemia cell line HL‐60, which is capable of differentiating through the FAB M2/M3 and M4/M5 immunophenotypes. These derivatives of HL‐60 harbored a B7‐2<sup>+</sup> subpopulation and recapitulated the distribution of B7 ligands previously reported in primary AML cases. B7‐2<sup>+</sup> AML cells significantly contributed to T‐cell responses. This costimulatory activity enabled helper (Th)‐cell activation, proliferation, and production of Th1‐associated cytokines. Conversely, even a short‐term incubation with stimulated T cells resulted in upregulation of inhibitory B7‐H1 (PD‐L1) and B7‐DC (PD‐L2), and downregulation of stimulatory B7‐H2 molecules on leukemia cells. Purified from iHL‐60‐T‐cell co‐cultures, these myeloid leukemia cells severely suppressed Th‐cell responses specifically through the PD‐1 pathway. In conclusion, Th‐cell responses can be directly supported by B7‐2<sup>+</sup> leukemia subpopulations. However, this interaction can facilitate the acquisition of a suppressive character that may contribute to immune evasion in myeloid leukemia.</p> </abstract> … (more)
- Is Part Of:
- European journal of immunology. Volume 43:Issue 3(2013:Mar.)
- Journal:
- European journal of immunology
- Issue:
- Volume 43:Issue 3(2013:Mar.)
- Issue Display:
- Volume 43, Issue 3 (2013)
- Year:
- 2013
- Volume:
- 43
- Issue:
- 3
- Issue Sort Value:
- 2013-0043-0003-0000
- Page Start:
- 747
- Page End:
- 757
- Publication Date:
- 2013-01-31
- Subjects:
- Immunology -- Periodicals
616.079 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1002/eji.201242814 ↗
- Languages:
- English
- ISSNs:
- 0014-2980
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 3829.730100
British Library DSC - BLDSS-3PM
British Library STI - ELD Digital store - Ingest File:
- 4357.xml