98%
921
2 minutes
20
Adenoviruses (HAdV) can cause life threatening infections, especially in paediatric patients after allogeneic stem cell transplantation (SCT). Yet, no effective antiviral medication is available. One treatment option is adoptive transfer of HAdV-specific T-cells from the graft donor into the patient. Especially CD4+ T-cells are critical to control HAdV infection. To allow for applicability of CD4+ T-cells in adoptive therapy, sufficient numbers of HAdV-specific T-cells with low levels of residual alloreactive T-cells are required. In this study, we explored the possibility to selectively expand and isolate functional HAdV-specific T-cells from PBMCs in response to 15-mer peptides using artificial antigen-presenting cells (aAPCs), composed of liposomes harbouring HAdV-peptide/HLA-Class-II complexes. HAdV-specific T-cells generated using this method produce mainly pro-inflammatory cytokines, express perforin and granzyme B, kill HAdV-infected cells effectively and are not alloreactive. Thus, the generation and isolation of HAdV-specific CD4+ T-cells seem a critical step towards specific adoptive therapy for HAdV infections after allogeneic SCT.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.clim.2013.01.002 | DOI Listing |
J Virol
May 2025
Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Human adenoviruses (HAdVs) cause self-limiting disease but are life-threatening to immunocompromised individuals. HAdV-C5 infects epithelial cells of the airways and eyes through aerosols, contaminated hands, or medical instruments, as well as fecal-oral contacts, gives rise to viremia, persisting in lymphoid cells of the gastrointestinal tract. Here, we show that pre-activated human primary blood-derived T cells can be infected with HAdV-C5 , upon incubation of the virus with a mixture of three distinct homotrimeric adapter proteins that target the virus to T cells.
View Article and Find Full Text PDFTransplant Cell Ther
June 2023
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Braunschweig, Germany. Electronic address:
Human adenovirus (HAdV) infection is a serious complication that can lead to significant morbidity and mortality, especially in immunocompromised pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Control and elimination of HAdV requires the presence of the respective antiviral T cells, and adoptive transfer of virus-specific T cells has become an important new treatment option for patients refractory to antiviral treatment. Although the adenoviral capsid protein hexon is known to be a major immunodominant T cell target across HAdV species, up to 30% of HAdV-seropositive donors show no T cell responses to the overlapping peptide pool spanning the entire protein.
View Article and Find Full Text PDFTranspl Infect Dis
February 2020
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Adenovirus (HAdV) infections confer a high risk of morbidity and mortality for immunocompromised patients after stem cell transplantation (SCT). Treatment with standard antiviral drugs is of limited efficacy and associated with a high rate of adverse effects. HAdV-specific T cells are crucial for sustained viral elimination and the efficacy of adoptive T-cell therapy with donor-derived HAdV-specific T cells has been reported by several investigators.
View Article and Find Full Text PDFJ Med Virol
August 2019
Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Introduction: Human adenovirus (HAdV) infection can cause substantial morbidity in kidney transplant (KT) recipients. Cell-mediated immunity plays an important role in controlling HAdV infection after KT.
Methods: We prospectively (January 2015 to June 2018) investigated the absolute lymphocyte count (ALC) and interferon-γ-producing CD4 and CD8 T cells at diagnosis and at viral clearance by an intracellular cytokine assay after stimulating with HAdV whole lysate, hexon, and penton proteins.
Bone Marrow Transplant
April 2017
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.