A mutation in X‐linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein–Barr virus‐specific T cells |
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| Authors: | E. Lopez‐Granados M. Stacey A.‐K. Kienzler S. Sierro C. B. Willberg C. P. Fox S. Rigaud H. M. Long A. D. Hislop A. B. Rickinson S. Patel S. Latour P. Klenerman H. Chapel |
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| Affiliation: | 1. Nuffield Department of Clinical Medicine, University of Oxford, , Oxford, UK;2. Weatherall Institute of Molecular Medicine, University of Oxford, , Oxford, UK;3. Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, , Oxford, UK;4. Biomedical Research Centre‐Translational Immunology Laboratory, University of Oxford, , Oxford, UK;5. Cancer Research UK Institute for Cancer Studies, University of Birmingham, , Birmingham, UK;6. Inserm UMR 1163, Laboratory of Lymphocyte Activation and EBV Susceptibility, University Paris Descartes Sorbonne Paris Cité, Institut Imagine, , Paris, France |
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| Abstract: | Mutations in the X‐linked inhibitor of apoptosis (XIAP) gene have been associated with XLP‐like disease, including recurrent Epstein–Barr virus (EBV)‐related haemophagocytic lymphohystiocytosis (HLH), but the immunopathogenic bases of EBV‐related disease in XIAP deficiency is unknown. We present the first analysis of EBV‐specific T cell responses in functional XIAP deficiency. In a family of patients with a novel mutation in XIAP (G466X) leading to a late‐truncated protein and varying clinical features, we identified gradual hypogammaglobulinaemia and large expansions of T cell subsets, including a prominent CD4+CD8+ population. Extensive ex‐vivo analyses showed that the expanded T cell subsets were dominated by EBV‐specific cells with conserved cytotoxic, proliferative and interferon (IFN)‐γ secretion capacity. The EBV load in blood fluctuated and was occasionally very high, indicating that the XIAPG466X mutation could impact upon EBV latency. XIAP deficiency may unravel a new immunopathogenic mechanism in EBV‐associated disease. |
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| Keywords: | cytotoxic T cells immunodeficiency diseases T cells viral |
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