Mumprecht, Sabine; Claus, Christina; Schürch, Christian; Pavelic, Viktor; Matter, Matthias S; Ochsenbein, Adrian F (2009). Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells. Blood, 113(19), pp. 4681-9. Washington, D.C.: American Society of Hematology 10.1182/blood-2008-05-156471
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Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease arising from a hematopoietic stem cell expressing the BCR/ABL fusion protein. Leukemic and dendritic cells (DCs) develop from the same transformed hematopoietic progenitors. How BCR/ABL interferes with the immunoregulatory function of DCs in vivo is unknown. We analyzed the function of BCR/ABL-expressing DCs in a retroviral-induced murine CML model using the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen. BCR/ABL-expressing DCs were found in bone marrow, thymus, spleen, lymph nodes, and blood of CML mice. They were characterized by a low maturation status and induced only limited expansion of naive and memory cytotoxic T lymphocytes (CTLs). In addition, immunization with in vitro-generated BCR/ABL-expressing DCs induced lower frequencies of specific CTLs than immunization with control DCs. BCR/ABL-expressing DCs preferentially homed to the thymus, whereas only few BCR/ABL-expressing DCs reached the spleen. Our results indicate that BCR/ABL-expressing DCs do not efficiently induce CML-specific T-cell responses resulting from low DC maturation and impaired homing to secondary lymphoid organs. In addition, BCR/ABL-expressing DCs in the thymus may contribute to CML-specific tolerance induction of specific CTLs.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Schürch, Christian, Ochsenbein, Adrian |
ISSN: |
0006-4971 |
Publisher: |
American Society of Hematology |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:11 |
Last Modified: |
05 Dec 2022 14:21 |
Publisher DOI: |
10.1182/blood-2008-05-156471 |
PubMed ID: |
19252140 |
Web of Science ID: |
000265910300031 |
BORIS DOI: |
10.7892/boris.31381 |
URI: |
https://boris.unibe.ch/id/eprint/31381 (FactScience: 195875) |
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