Projects per year
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 XIAP(G466X) mutation could impact upon EBV latency. XIAP deficiency may unravel a new immunopathogenic mechanism in EBV-associated disease.
- Cells, Cultured
- Herpesvirus 4, Human
- Immunologic Memory
- Viral Load
- X-Linked Inhibitor of Apoptosis Protein
FingerprintDive into the research topics of 'A mutation in X-linked inhibitor of apoptosis (G466X) leads to memory inflation of Epstein-Barr virus-specific T cells'. Together they form a unique fingerprint.
- 1 Finished
Cellular Immunity to Herpesvirus Infections: Studies with Epstein-Barr Virus (EBV) and Human Cytomegalovirus (CMV)
Rickinson, A., Moss, P. & Rowe, M.
1/09/10 → 31/08/15
Project: Research Councils