{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T08:11:27Z","timestamp":1744359087537},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Antigen\u2010specific 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\u2010versus\u2010host disease (GVHD). Non\u2010specific immune\u2010ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope\u2010specific T cells could theoretically ameliorate T\u2010cell\u2010mediated pathology while preserving the rest of the host immune function. In this study we investigated whether it is possible to destroy specific unwanted antigen\u2010specific T cells by incubating polyclonal T\u2010cell populations with major histocompatibility complex (MHC) tetramers that are conjugated to the ribosomal\u2010inactivating toxin, saporin. This strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)\u2010specific CD8 T cells with no observable bystander toxicity <jats:italic>in vitro<\/jats:italic>. Moreover, in a model of transferable T\u2010cell\u2010dependent neurological disease induced by intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the targeted killing of LCMV\u2010specific CD8 T cells extended the survival of mice or fully prevented their death, depending on the dose of cells transferred. In addition, the tetramer\u2013 saporin conjugate also reduced liver damage in a model of donor T\u2010cell\u2010mediated hepatic destruction. These data provide a proof of principle that MHC tetramers could be exploited for the elimination or clinical manipulation of T\u2010cell 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\u2010cell responses, especially in immunocompromised hosts who receive adoptive cell transfers with many potential alloreactive cells.<\/jats:p>","DOI":"10.1111\/j.1365-2567.2009.03080.x","type":"journal-article","created":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T06:58:30Z","timestamp":1234853910000},"page":"164-171","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["T\u2010cell reconstitution without T\u2010cell immunopathology in two models of T\u2010cell\u2010mediated tissue 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