Program DHC-Virtual
20 - 21 January 2021
Abstracts Immunology session 4
Abstract
Skewing of the antigen-specific T cell response in CLL
21 January
10:36 10:48
F. Peters
Paper

Chronic Lymphocytic Leukemia Induces Skewing of Antigen-Specific T-cell Responses Towards a Dysfunctional Short-Lived Effector Phenotype

Fleur S. Peters (1,2), Anne W.J. Martens (1,2), Inga Kavazovic (3), Ramon Arens (4), Aldo Jongejan (5), Perry D. Moerland (5), Eric Eldering (1), Gerritje J.W. van der Windt (1,2), Felix M. Wensveen (3), Arnon P. Kater (2)
(1) Amsterdam UMC, Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands, (2) Amsterdam UMC, Department of Hematology, Cancer Center Amsterdam, Amsterdam, The Netherlands, (3) University of Rijeka, Department of Histology and Embryology, Faculty of Medicine, Rijeka, Croatia, (4) Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, Leiden, The Netherlands, (5) Amsterdam UMC, Department of Epidemiology and Data Science, Amsterdam, The Netherlands
No potential conflicts of interest
Introduction

The TCL1 mouse model displays similar features of T-cell dysfunction as observed in chronic lymphocytic leukemia (CLL) patients and provides an excellent model to study antigen-specific CD8+ T-cell response in the context of CLL. 

Methods

We developed a model to study antigen-specific responses in the TCL1 adoptive transfer model. Following development of leukemia, mice were injected with OT-I cells and infected with mCMV-OVA.  

Results

Seven days after infection, we observed skewing of both the endogenous CD8 compartment as well as the adoptively transferred OT-I cells towards a short-lived effector phenotype (KLRG1+CD127-) in CLL mice compared to wild-type mice. This was associated with enhanced expression of the effector-associated transcription factor T-bet, and reduced expression of memory-associated transcription factor Bcl-6. Restimulation of  OT-I cells resulted in decreased cytokine production and degranulation of the CLL derived OT-I cells. These phenotypic and functional characteristics were accompanied by genome-wide chromatin remodeling and altered gene expression profiles, which will be further presented during the meeting. 

Conclusion

Our results demonstrate that there is a CLL-dependent effect on acute (non-CLL) antigen-specific immune responses, driving T-cells towards a functionally impaired effector phenotype. This study provides clues for better understanding T-cell responses dysfunction in CLL, possibly leading to improved T-cell therapy.

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