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:
Notes: Blood -- Cited By (since 1996):19 -- Export Date: 16 June 2014 -- CODEN: BLOOA -- Source: Scopus
Altmetric Score
MSK Authors
  1. William Bornmann
    107 Bornmann
  2. Rui Rong Yuan
    4 Yuan
  3. Michael R Mcdevitt
    117 Mcdevitt
  4. Eric Pamer
    237 Pamer
  5. Phillip Wong
    31 Wong
  6. Ingrid Leiner
    44 Leiner
  7. Richard O'Reilly
    459 O'Reilly