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dc.contributor.authorSchwarz, Edward Michael
dc.date.accessioned2018-07-12T18:39:31Z
dc.date.available2018-07-12T18:39:31Z
dc.date.issued1993
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 54-03, Section: B, page: 1319.;Advisors: Barry R. Bloom.
dc.identifier.urihttp://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9320796
dc.identifier.urihttps://hdl.handle.net/20.500.12202/3485
dc.description.abstractIL-2 and IL-4 are lymphokines produced by different functional T-cell subsets, T{dollar}\sb{lcub}\rm H{rcub}{dollar}1 and T{dollar}\sb{lcub}\rm H{rcub}{dollar}2 respectively, and reciprocally negatively regulate each other. To elucidate the molecular mechanism of IL-4 immunosuppression we studied its inhibitory effects on an essential T-cell growth factor, IL-2. IL-4 pretreatment of the leukemic Jurkat T-cell line for 24hr followed by stimulation with PMA and ionomycin resulted in a 4 fold decrease in steady-state IL-2 mRNA in Northern analyses. A comparable decrease in mRNA levels was seen in IL-4 pretreated, peripheral T-cells stimulated by anti-CD3. A CD28 second signal eliminates this inhibition. Since the IL-2 gene promoter has been extensively studied, we were able to test the effect of IL-4 on the individual enhancer elements, using {dollar}\beta{dollar}-galactosidase as a reporter. One of these enhancer elements, NFIL-2B, showed a decrease of 50% {dollar}\beta{dollar}-galactosidase activity when the transformed cells were pretreated with IL-4. Electrophoretic mobility shift assays using a DNA oligomer containing the NFIL-2B binding site indicated that pretreatment with IL-4 inhibited the formation of the NFIL-2B complex, and that the NFIL-2B complex contains at least one other DNA binding factor that is distinct from AP-1. These results suggest that IL-4 may regulate development and function of T cell subsets involved in cell-mediated immunity, in part by inhibiting one or more factors required for transcription of the IL-2 gene.
dc.publisherProQuest Dissertations & Theses
dc.subjectImmunology.
dc.subjectCellular biology.
dc.titleOn the molecular mechanism of IL-4 immunosuppression and the characterization of NFIL-2B
dc.typeDissertation


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