?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F34548%2F&rft.title=Tim-3+co-stimulation+promotes+short-lived+effector+T+cells%2C+restricts+memory+precursors%2C+and+is+dispensable+for+T+cell+exhaustion&rft.creator=Avery%2C+Lyndsay&rft.description=Tim-3+is+highly+expressed+on+a+subset+of+T+cells+during+T+cell+exhaustion%2C+in+settings+of+chronic+viral+infection+and+in+tumors.+Using+LCMV+Clone+13%2C+a+model+for+chronic+infection%2C+we+have+found+that+Tim-3+is+neither+necessary+nor+sufficient+for+the+development+of+T+cell+exhaustion.+Nonetheless%2C+expression+of+Tim-3+was+sufficient+to+drive+resistance+to+PD-L1+blockade+therapy+during+chronic+infection.+Strikingly%2C+expression+of+Tim-3+promoted+the+development+of+short-term+effector+T+cells%2C+at+the+expense+of+memory+precursor+development%2C+following+acute+infection+with+LCMV-Armstrong.+These+effects+were+accompanied+by+increased+Akt%2FmTOR+signaling+in+T+cells+with+endogenous+or+ectopically+expressed+Tim-3.+Conversely%2C+Akt%2FmTOR+signaling+was+reduced+in+effector+T+cells+from+Tim-3+deficient+mice.+Thus%2C+Tim-3%2C+while+essential+for+optimal+effector+T+cell+responses%2C+but+may+also+contribute+to+T+cell+exhaustion+is+restricting+the+development+of+long-lived+memory+T+cells.+Taken+together%2C+our+results+suggest+that+Tim-3+is+more+similar+to+co-stimulatory+receptors+that+are+upregulated+following+T+cell+activation%2C+rather+than+dominant+inhibitory+proteins+such+as+PD-1.+These+findings+have+significant+implications+for+the+development+of+anti-Tim-3+antibodies+as+immunotherapy+agents+for+the+treatment+of+cancer%2C+infections%2C+and+other+matters+of+public+health.&rft.date=2018-09-17&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F34548%2F1%2FAveryL_ETD_June2018.pdf&rft.identifier=++Avery%2C+Lyndsay++(2018)+Tim-3+co-stimulation+promotes+short-lived+effector+T+cells%2C+restricts+memory+precursors%2C+and+is+dispensable+for+T+cell+exhaustion.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++