Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele Journal Article


Authors: Papanicolaou, G. A.; Latouche, J. B.; Tan, C.; Dupont, J.; Stiles, J.; Pamer, E. G.; Sadelain, M.
Article Title: Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele
Abstract: Cytomegalovirus (CMV) is a major threat in patients undergoing allogeneic bone marrow transplantation. The adoptive transfer of CMV-specific cytotoxic T lymphocytes (CTLs) expanded from the blood of CMV-seropositive donors has been shown to effectively control CMV infection. However, the requirement for safe and effective antigen-presenting cells (APCs) for each patient precludes broad applicability of this successful form of therapy. Here we analyze the ability of artificial APCs (AAPCs) to activate and expand CMV-specific CTLs from peripheral blood of seropositive HLA A2.1+ donors. We demonstrate that AAPCs expressing the CMV P495 peptide or the full-length pp65 protein stimulate P495-specific CTLs at least as effectively as autologous, peptide-pulsed, peripheral blood mononuclear cells or EBV-transformed B cells. Starting from 100 mL of blood, the AAPCs reliably yield clinically relevant CTL numbers after a single stimulation. CTLs activated on AAPCs effectively kill CMV-infected fibroblasts and have a Tc1 memory effector phenotype identical to that of CTLs generated with autologous APCs. AAPCs thus offer a rapid, controlled, convenient, and highly reproducible system for expanding CMV-specific CTLs. Furthermore, the CTL expansion obtained with AAPCs encoding full-length pp65 indicates that AAPCs may be used to present known as well as unknown CTL epitopes in the context of the AAPC's HLA. © 2003 by The American Society of Hematology.
Keywords: controlled study; protein expression; unclassified drug; human cell; nonhuman; flow cytometry; animal cell; phenotype; cell division; protein; allogenic bone marrow transplantation; b lymphocyte; blood; cytokines; mononuclear cell; epitope; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; fibroblast; adoptive transfer; immunophenotyping; cell count; reliability; serodiagnosis; fetus; memory cell; bone marrow transplantation; infection control; cytomegalovirus infection; matrix protein; antigen presenting cell; cytomegalovirus; immunotherapy, adoptive; antigen-presenting cells; t lymphocyte activation; immunologic memory; cell killing; hla system; hla a2 antigen; hla-a2 antigen; blood donor; cytomegalovirus infections; humans; human; priority journal; article; protein p495; protein pp65
Journal Title: Blood
Volume: 102
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2003-10-01
Start Page: 2498
End Page: 2505
Language: English
DOI: 10.1182/blood-2003-02-0345
PUBMED: 12805061
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Jakob Dupont
    65 Dupont
  2. Eric Pamer
    278 Pamer
  3. Michel W J Sadelain
    540 Sadelain
  4. Jeffrey Stiles
    26 Stiles
  5. Cuiwen   Tan
    11 Tan