Cytokine Expression Pattern of CD4+ Memory T Cells from Children with Onset and Long-Term Type 1 Diabetes Are Promoted By IL-7

Presentation Number: SUN 598
Date of Presentation: April 2nd, 2017

Julia Seyfarth*1, Katharina Förtsch1, Hans-Jürgen Laws2, Beate Karges3, Ertan Mayatepek1, Thomas Meissner4 and Marc Jacobsen1
1University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany, 2University Children´s Hospital, Düsseldorf, 3RWTH Aachen University, German Center for Diabetes Research (DZD), Aachen, Germany, 4University Children's Hospital, Heinrich Heine University Düsseldorf, German Center for Diabetes Research (DZD), Düsseldorf, Germany

Abstract

CD4+effector T cells play a central role in the development of type 1 diabetes. Interleukin-7 (IL-7) promotes generation of autoimmune effector T cells and increased IL-7 availability is associated with type 1 diabetes. Immune pathology differences during symptomatic stages of type 1 diabetes disease course remain elusive. Here we addressed the question if the general T-cell cytokine expression profile differs between onset and long term type 1 diabetes disease stages and whether IL-7 sensitivity and promoted T-cell functions change during type 1 diabetes disease course.

We compared memory CD4+T-cell cytokine expression and IL-7 sensitivity between patients with type 1 diabetes at clinical onset (n=25), long-term symptomatic disease (median duration 4.5 years, n=19), and matched healthy controls (n=21). Sample collection was performed in the framework of the pediatric diabetes biomaterial bank in DZD (German Center for Diabetes Research). The effect of IL-7 co-stimulation on T-cell activation dependent cytokine expression and differences between the study groups were assessed by intracellular cytokine staining and flow cytometric analysis of donors PBMC.

We detected higher proportions of cytokine (i.e. IFNg, TNFα, IL-2, IL-17) and activation marker (CD69, CD40L) expressing CD4+ T cells in children with type 1 diabetes as compared to healthy controls. Qualitative cytokine pattern analyses detected significantly increased TNFα and decreased Interleukin-2 expressing T-cell proportions in long-term type 1 diabetes patients as compared to healthy controls. IL-7 mediated T-cell co-stimulation induced absolute and qualitative cytokine expression differences highly similar to type 1 diabetes specific pattern. Furthermore, CD4+T cells from children with long term type 1 diabetes were more sensitive to IL-7 stimulation, showing increased activation marker and cytokine (i.e. TNFα) expression as compared to healthy controls.

We conclude that symptomatic type 1 diabetes patients at clinical onset and long-term follow up differed in memory T-cell responses and IL-7 sensitivity. Since pathogenic pattern even increased during disease course, aberrant CD4+ T-cell responses at later symptomatic stages may affect disease severity and susceptibility against type 1 diabetes associated autoimmune diseases.

 

Nothing to Disclose: JS, KF, HJL, BK, EM, TM, MJ