Immune profiling and functional analysis of NK and T cells in ataxia telangiectasia.

Autor:	Graafen L; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Experimental Immnology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany., Heinze A; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Experimental Immnology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany., Albinger N; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Experimental Immnology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany., Salzmann-Manrique E; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Ganß F; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Experimental Immnology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany.; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany., Hünecke S; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Cappel C; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Wölke S; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Frankfurt am Main, Germany., Donath H; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Frankfurt am Main, Germany., Trischler J; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Frankfurt am Main, Germany., Theilen TM; Department of Pediatric Surgery and Urology, Goethe University Frankfurt, Frankfurt, Germany., Heller C; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Königs C; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Ehl S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bader P; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Klingebiel T; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany., Klusmann JH; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany., Zielen S; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Frankfurt am Main, Germany., Schubert R; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, Goethe University Frankfurt, Frankfurt am Main, Germany., Ullrich E; Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.; Department of Pediatrics, Experimental Immnology and Cell Therapy, Goethe University Frankfurt, Frankfurt am Main, Germany.; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.; German Cancer Consortium (DKTK) Partner Site Frankfurt/Mainz, Frankfurt am Main, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Aug 06; Vol. 15, pp. 1377955. Date of Electronic Publication: 2024 Aug 06 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1377955
Abstrakt:	Ataxia telangiectasia (AT) is a rare autosomal-recessive disorder characterized by profound neurodegeneration, combined immunodeficiency, and an increased risk for malignant diseases. Treatment options for AT are limited, and the long-term survival prognosis for patients remains grim, primarily due to the emergence of chronic respiratory pathologies, malignancies, and neurological complications. Understanding the dysregulation of the immune system in AT is fundamental for the development of novel treatment strategies. In this context, we performed a retrospective longitudinal immunemonitoring of lymphocyte subset distribution in a cohort of AT patients ( n = 65). Furthermore, we performed FACS analyses of peripheral blood mononuclear cells from a subgroup of 12 AT patients to examine NK and T cells for the expression of activating and functional markers. We observed reduced levels of peripheral blood CD3 + CD8 + cytotoxic T cells, CD3 + CD4 + T helper cells, and CD19 + B cells, whereas the amount of CD3 -- CD56 + NK cells and CD3 + CD56 + NKT-like cells was similar compared with age-matched controls. Notably, there was no association between the age-dependent kinetic of T-, B-, or NK-cell counts and the occurrence of malignancy in AT patients. Additionally, 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 AT with notably higher expression levels of IFN-γ, CD107a, TRAIL, and FasL. Together, these findings imply function alterations in AT lymphocytes, specifically in T and NK cells, shedding light on potential pathways for innovative therapies. Competing Interests: EU has no COIs directly related to this manuscript. EU has a sponsored research project with Gilead, BMS, and CRIION. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Graafen, Heinze, Albinger, Salzmann-Manrique, Ganß, Hünecke, Cappel, Wölke, Donath, Trischler, Theilen, Heller, Königs, Ehl, Bader, Klingebiel, Klusmann, Zielen, Schubert and Ullrich.)
Databáze:	MEDLINE
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