Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers Journal Article

  


Authors: Yuan, R. R.; Wong, P.; McDevitt, M. R.; Doubrovina, E.; Leiner, I.; Bornmann, W.; O'reilly, R.; Pamer, E. G.; Scheinberg, D. A.
Article Title: Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers
Abstract: Immunosuppressive agents in current use are nonspecific. The capacity to delete specific CD8 T-cell clones of unique specificity could prove to be a powerful tool for dissecting the precise role of CD8+ T cells in human disease and could form the basis for a safe, highly selective therapy of autoimmune disorders. Major histocompatibility complex (MHC) tetramers (multimeric complexes capable of binding to specific CD8 T-cell clones) were conjugated to 225Ac (an alpha-emitting atomic nanogenerator, capable of single-hit killing from the cell surface) to create an agent for CD8 T-cell clonal deletion. The "suicide" tetramers specifically bound to, killed, and reduced the function of their cognate CD8 T cells (either human anti-Epstein-Barr virus (EBV) or mouse anti-Listeria in 2 model systems) while leaving the nonspecific control CD8 T-cell populations unharmed. Such an approach may allow a pathway to selective ablation of pathogenic T-cell clones ex vivo or in vivo without disturbing general immune function. © 2004 by The American Society of Hematology.
Keywords: controlled study; gene deletion; nonhuman; flow cytometry; cd8 antigen; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; cell line; in vitro study; immunological tolerance; substrate specificity; histocompatibility antigens class i; peptides; temperature; autoimmune disease; major histocompatibility complex; ex vivo study; clone cells; t lymphocyte subpopulation; epstein barr virus; lymphocyte count; cell killing; immunosuppressive agent; tetramer; humans; priority journal; article
Journal Title: Blood
Volume: 104
Issue: 8
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2004-10-15
Start Page: 2397
End Page: 2402
Language: English
DOI: 10.1182/blood-2004-01-0324
PROVIDER: scopus
PUBMED: 15217835
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-4944254829&partnerID=40&md5=89f44d498e9822d81a4a2403bd43b373
Notes: Blood -- Cited By (since 1996):19 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus
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MSK Authors
  1. William Bornmann
    112 Bornmann
  2. Rui Rong Yuan
    4 Yuan
  3. Michael R Mcdevitt
    144 Mcdevitt
  4. Eric Pamer
    283 Pamer
  5. Phillip Wong
    79 Wong
  6. Ingrid Leiner
    49 Leiner
  7. Ekaterina Doubrovina
    101 Doubrovina
  8. David Scheinberg
    499 Scheinberg
  9. Richard O'Reilly
    747 O'Reilly
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