Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells

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

[img] Text
4681.full.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

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 and Ochsenbein, Adrian

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:11

Last Modified:

22 Dec 2015 09:19

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)

Actions (login required)

Edit item Edit item
Provide Feedback