Faculty Collaboration Database

Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct viruses for the prophylaxis of patients receiving an allogeneic bone marrow transplant. Bone Marrow Transplant 2001 Jan;27(1):53-64

Date

03/13/2001

Pubmed ID

11244438

DOI

10.1038/sj.bmt.1702752

Scopus ID

2-s2.0-0035141371 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

Human adenovirus (AdV) infection and EBV-lymphoproliferative disease (LPD) are serious complications following allogeneic stem cell transplantation. In the healthy individual these viruses cause minor, self-limiting diseases but in the immunocompromised patient they are responsible for significant morbidity and mortality. The limitations of anti-viral drugs and a better understanding of the cellular immune response to viral pathogens have prompted interest in developing adoptive immunotherapy for transplant patients. Ex vivo expanded cytotoxic T lymphocytes (CTLs) specific for EBV have been used effectively both as prophylaxis against EBV-LPD and as treatment of established EBV+ lymphoma. To generate CTLs specific for AdV, we infected immature dendritic cells with virus, in the presence of lipid, and subsequently used these cells to stimulate PBMNCs. Cytotoxicity assays showed that the resulting CTLs specifically lysed AdV-expressing targets and that this was mediated predominantly by CD4+ T cells. To generate CTLs specific for both AdV and EBV, we developed a CD40 ligand co-culture system to infect B-lymphoblastoid cell lines (LCLs) with high efficiency. PBMNCs from healthy AdV-seropositive donors were stimulated weekly with autologous AdV+-LCLs. Chromium release assays demonstrated that the resultant CTLs had specificity against both EBV and AdV and that this was mediated by both CD4+ and CD8+ T cells. Our findings have potential implications for post-transplant AdV and EBV immunotherapy in recipients of allogeneic stem cell transplants.

Author List

Regn S, Raffegerst S, Chen X, Schendel D, Kolb HJ, Roskrow M

Author

Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoviridae
Antigen Presentation
Antigen-Presenting Cells
Bone Marrow Transplantation
Cell Culture Techniques
Coculture Techniques
Dendritic Cells
Herpesvirus 4, Human
Humans
Immunophenotyping
Immunotherapy, Adoptive
Lymphocyte Culture Test, Mixed
T-Lymphocytes, Cytotoxic
Transplantation, Homologous
Viruses