Adaptation of NK cell function in ATM deficiency
Hematology, Oncology
Final Report Abstract
The research project “Adaptation of NK cell function in ATM deficiency” address the immune cell adaptation in A-T patients, with a focus on natural killer (NK) cell function. While previous studies of immune cells in A-T patients mainly addressed T cell development and T cell function, we here aim to investigate the maturation and functionality of NK cells to assess their contribution to immunodeficiency and malignant diseases in A -T. The main objective in the project part performed by the team of E. Ullrich was to investigate the functionality of NK cells from peripheral blood of A-T patients in different stages of disease. In this context, we performed a retrospective longitudinal immune monitoring of lymphocyte subset distribution in a cohort of 65 A-T patients. We observed reduced levels of peripheral blood CD3+CD8+ cytotoxic T cells, CD3+CD4+ T helper cells and CD19+ B cells, while the amount of CD3-CD56+ NK cells and CD3+CD56+ NKT-like cells was similar compared to age-matched controls. Furthermore, we prospectively performed FACS analyses of peripheral blood mononuclear cells from a subgroup of 12 A-T patients to examine NK and T cells for the expression of activating and functional markers. Our results indicate an altered NK and T cell response to cytokine stimulation in AT with increased levels of TRAIL, FasL and CD16 expression in NK cells, as well as an elevated activation level of T cells in A-T with higher expression levels of IFN-γ, CD107a, TRAIL and FasL. Together these findings imply function alterations in A-T lymphocytes, specifically in T and NK cells, shedding light on potential pathways for innovative therapies. This project has provided important insights into the functioning of NK cells and their ability to control tumors in A-T patients and hopefully paves the way not only for understanding the underlying mechanisms but also for new therapeutic strategies in A-T.
Publications
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Tracking of Infused Mesenchymal Stem Cells in Injured Pulmonary Tissue in Atm-Deficient Mice. Cells, 9(6), 1444.
Baer, Patrick C.; Sann, Julia; Duecker, Ruth Pia; Ullrich, Evelyn; Geiger, Helmut; Bader, Peter; Zielen, Stefan & Schubert, Ralf
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Immune profiling and functional analysis of NK and T cells in ataxia telangiectasia. Frontiers in Immunology, 15.
Graafen, Lea; Heinze, Annekathrin; Albinger, Nawid; Salzmann-Manrique, Emilia; Ganß, Franziska; Hünecke, Sabine; Cappel, Claudia; Wölke, Sandra; Donath, Helena; Trischler, Jordis; Theilen, Till-Martin; Heller, Christine; Königs, Christoph; Ehl, Stephan; Bader, Peter; Klingebiel, Thomas; Klusmann, Jan-Henning; Zielen, Stefan; Schubert, Ralf & Ullrich, Evelyn
