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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