Authors contributed equally to this work.
Naive Tumour-Specific CD4+ T Cells were Efficiently Primed in Acute Lymphoblastic Leukaemia
Article first published online: 21 AUG 2014
© 2014 John Wiley & Sons Ltd
Scandinavian Journal of Immunology
Volume 80, Issue 3, pages 161–168, September 2014
How to Cite
Noyan, F., Lieke, T., Taubert, R., Sievers, M., Dywicki, J., Hapke, M., Falk, C. S., Manns, M. P., Jaeckel, E. and Hardtke-Wolenski, M. (2014), Naive Tumour-Specific CD4+ T Cells were Efficiently Primed in Acute Lymphoblastic Leukaemia. Scandinavian Journal of Immunology, 80: 161–168. doi: 10.1111/sji.12198
- Issue published online: 21 AUG 2014
- Article first published online: 21 AUG 2014
- Accepted manuscript online: 9 JUN 2014 05:03AM EST
- Manuscript Accepted: 21 MAY 2014
- Manuscript Received: 24 MAR 2014
- Hannover Medical School
The recognition and neutralization of tumour cells is one of the big challenges in immunity. The immune system has to recognize syngeneic tumour cells and has to be primed and respond in an adequate manner. Priming of a leukaemia-specific immune response is a crucial step in tumour immunology that can mislead to tumour tolerance either by T cell ignorance, deletion or Treg induction. To resemble the situation of acute lymphoblastic leukaemia (ALL) in patients, we used the murine BALB/c model with syngeneic BM185 tumour cells. We established a tumour cell line that expresses the neo-antigen ovalbumin (BM185-OVA/GFP) to allow the application of T cell receptor transgenic, antigen-specific CD4+ T cells. Here, we demonstrate that effective anti-ALL immunity can be established by in vivo priming of CD4+ T cells that is sufficient to differentiate into effector cells. Yet they failed to control tumour alone, but initiated a Th1 response. An efficient tumour clearance was dependent on both antigen-specific CD4+ T cells and CD8+ effector T cells from the endogenous repertoire. The tolerogeneic milieu was characterized by increased Tregs numbers and elevated IL-10 level. Tregs hamper effective antitumour immune response, but their depletion did not result in reduced tumour growth. In contrast, neutralization of IL-10 improved median mouse survival. Future therapies should focus on establishing a strong CD4+ T cells response, either by adjuvant or by adoptive transfer.