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• W2117270568 abstract "Summary Antigen‐specific T cells play a pivotal role in adaptive immune responses. However, they also contribute to the progression of a variety of diseases including autoimmune disorders, graft rejection and graft‐versus‐host disease (GVHD). Non‐specific immune‐ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope‐specific T cells could theoretically ameliorate T‐cell‐mediated pathology while preserving the rest of the host immune function. In this study we investigated whether it is possible to destroy specific unwanted antigen‐specific T cells by incubating polyclonal T‐cell populations with major histocompatibility complex (MHC) tetramers that are conjugated to the ribosomal‐inactivating toxin, saporin. This strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)‐specific CD8 T cells with no observable bystander toxicity in vitro . Moreover, in a model of transferable T‐cell‐dependent neurological disease induced by intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the targeted killing of LCMV‐specific CD8 T cells extended the survival of mice or fully prevented their death, depending on the dose of cells transferred. In addition, the tetramer– saporin conjugate also reduced liver damage in a model of donor T‐cell‐mediated hepatic destruction. These data provide a proof of principle that MHC tetramers could be exploited for the elimination or clinical manipulation of T‐cell responses by linking effector molecules (a toxin in this case) to MHC tetramers. Also, the results suggest that it may be feasible to remodel T‐cell responses, especially in immunocompromised hosts who receive adoptive cell transfers with many potential alloreactive cells." @default.
• W2117270568 created "2016-06-24" @default.
• W2117270568 creator A5016808814 @default.
• W2117270568 creator A5022314324 @default.
• W2117270568 creator A5050735501 @default.
• W2117270568 date "2009-09-04" @default.
• W2117270568 modified "2023-09-30" @default.
• W2117270568 title "T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction" @default.
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• W2117270568 doi "https://doi.org/10.1111/j.1365-2567.2009.03080.x" @default.
• W2117270568 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2767306" @default.
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