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Immunology

Ex vivo priming of CD4 T cells converts immunological tolerance into effective antitumor immunity in a murine model of acute lymphoblastic leukemia

Leukemia volume 22, pages 2070–2079 (2008)Cite this article

Abstract

Tumor escape mechanisms in leukemia are not well defined. To dissect immunological mechanisms responsible for immune tolerance toward leukemia, we established a murine model system allowing clonotypic analysis of leukemia-specific CD4 T cells recognizing ovalbumin (OVA). Upon i.v. injection of genetically engineered leukemia cells, dendritic cells (DCs) engulfed, processed and presented OVA to OVA-specific CD4 T cells. Consequently, leukemia-specific T cells were primed in vivo as shown by expression of activation markers and proliferative responses. However, in spite of detectable CD4 T cell responses in vitro and in vivo, no effective anti-leukemia immunity was established. In contrast, adoptively transferred DO11.10 T cells that were primed ex vivo mediated effective antitumor immunity. Furthermore, ex vivo primed DO11.10 T cells showed high expression of Th1 cytokines (interferon-γ, tumor necrosis factor-α and interleukin-2) whereas in vivo primed OVA-specific CD4 T cells showed incomplete differentiation (proliferation without cytokine production). We conclude that activated T cells lacking effector function develop through incomplete differentiation in leukemia-bearing mice. Thus, priming conditions of leukemia-specific CD4 T cells critically determines the balance between immunity or tolerance toward leukemia.

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Acknowledgements

We thank Renata Stripecke for BM185 cells, Thomas Kamradt for DO11.10 mice, Matthias Ballmaier for cell sorting, Inga Sandrock for excellent technical support, Ricardo Dewey and Chozhavendan Rathinam for helpful discussions and Karl Welte for continuous support. This study was supported by the Wilhelm-Sander-Foundation 0172 5431807 and DFG (SFB738).

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  1. A N Hegazy

    Present address: 2Present address: German Arthritis Research Center, Chariteplatz 1, Berlin 10117, Germany,

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  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    A N Hegazy & C Klein

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Correspondence to C Klein.

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Hegazy, A., Klein, C. Ex vivo priming of CD4 T cells converts immunological tolerance into effective antitumor immunity in a murine model of acute lymphoblastic leukemia. Leukemia 22, 2070–2079 (2008). https://doi.org/10.1038/leu.2008.193

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