EBV-associated mononucleosis leads to long-term global deficit in T-cell responsiveness to IL-15
- 1 July 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (1), 11-18
- https://doi.org/10.1182/blood-2006-01-0144
Abstract
In mice, interleukin-7 (IL-7) and IL-15 are involved in T-cell homeostasis and the maintenance of immunologic memory. Here, we follow virus-induced responses in infectious mononucleosis (IM) patients from primary Epstein-Barr virus (EBV) infection into long-term virus carriage, monitoring IL-7 and IL-15 receptor (IL-R) expression by antibody staining and cytokine responsiveness by STAT5 phosphorylation and in vitro proliferation. Expression of IL-7Rα was lost from all CD8+ T cells, including EBV epitope-specific populations, during acute IM. Thereafter, expression recovered quickly on total CD8+ cells but slowly and incompletely on EBV-specific memory cells. Expression of IL-15Rα was also lost in acute IM and remained undetectable thereafter not just on EBV-specific CD8+ populations but on the whole peripheral T- and natural killer (NK)-cell pool. This deficit, correlating with defective IL-15 responsiveness in vitro, was consistently observed in patients up to 14 years after IM but not in patients after cytomegalovirus (CMV)-associated mononucleosis, or in healthy EBV carriers with no history of IM, or in EBV-naive individuals. By permanently scarring the immune system, symptomatic primary EBV infection provides a unique cohort of patients through which to study the effects of impaired IL-15 signaling on human lymphocyte functions in vitro and in vivo. (Blood. 2006;108:11-18)Keywords
This publication has 39 references indexed in Scilit:
- The immune response to primary EBV infection: a role for natural killer cellsBritish Journal of Haematology, 2005
- Long‐Term Shedding of Infectious Epstein‐Barr Virus after Infectious MononucleosisThe Journal of Infectious Diseases, 2005
- IL-7: maintaining T-cell memory and achieving homeostasisTrends in Immunology, 2005
- Central Memory and Effector Memory T Cell Subsets: Function, Generation, and MaintenanceAnnual Review of Immunology, 2004
- Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cellsNature Immunology, 2003
- Characteristics of Hodgkin's Lymphoma after Infectious MononucleosisNew England Journal of Medicine, 2003
- Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokinesBlood, 2003
- IL-15Rα Recycles and Presents IL-15 In trans to Neighboring CellsImmunity, 2002
- Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T CellsThe Journal of Experimental Medicine, 2002
- Epitope-specific Evolution of Human CD8+ T Cell Responses from Primary to Persistent Phases of Epstein-Barr Virus InfectionThe Journal of Experimental Medicine, 2002