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pubmed-article:1987288pubmed:dateCreated1991-2-20lld:pubmed
pubmed-article:1987288pubmed:abstractTextInterleukin 2 (IL-2)-activated peripheral blood mononuclear cells (PBMC) have been reported to lyse tumor cells while essentially sparing normal cells in vitro. This report concerns IL-2-induced anti-keratinocyte (anti-KC) cytotoxic effectors that lyse normal human keratinocytes (KC) in vitro. Effectors were generated by culturing PBMC for 1-8 d in various concentrations of recombinant IL-2 and then assayed against 51Cr-labeled targets. Effectors stimulated with 10(3) U/ml of IL-2 for 8 d readily lysed adherent or trypsinized autologous or allogeneic KC cultured in serum-free medium. Induction of anti-KC effectors was IL-2 dose-dependent, with as little as 12-25 U/ml of IL-2 inducing increased anti-KC activity after 24 h of treatment. Although anti-KC activity was increased after overnight culture in IL-2, maximal effector potency in terms of lytic units (LU) per 10(6) effector cells required 4 d of IL-2 treatment. Maximal effector yield in terms of LU per input PBMC occurred after 8 d of IL-2 treatment. Antibody plus complement depletion studies showed that the anti-KC effectors predominantly have a CD16 --/CD3 --/CD2+ phenotype. A natural killer (NK)-like specificity of the effectors was suggested by two findings: unlabeled K562 cells totally inhibited lysis of 51Cr-KC in cold target competition assays, and interferon gamma (IFN-g) treatment (2.5 U/ml-500 U/ml of recombinant IFN-g for 48-72 h) down-regulated KC susceptibility to lysis by these effectors. Thus, IL-2 treatment of PBMC induces non-T cell, natural killer-like effectors that can lyse both autologous and allogeneic KC. Furthermore, KC resemble other cell types that become resistant to non-MHC-restricted lysis after treatment with IFN-g. Finally, the contrasting effects of IFN-g treatment on KC lysis by these effectors, as opposed to lysis by specific T cells, suggests that IFN-g could promote a shift from non-MHC-restricted to MHC-restricted KC lysis during epidermal immune responses in vivo.lld:pubmed
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pubmed-article:1987288pubmed:issn0022-202Xlld:pubmed
pubmed-article:1987288pubmed:authorpubmed-author:SymingtonF...lld:pubmed
pubmed-article:1987288pubmed:authorpubmed-author:SantosE BEBlld:pubmed
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pubmed-article:1987288pubmed:pagination127-33lld:pubmed
pubmed-article:1987288pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:1987288pubmed:year1991lld:pubmed
pubmed-article:1987288pubmed:articleTitleLysis of keratinocytes by IL-2-activated peripheral blood lymphocytes.lld:pubmed
pubmed-article:1987288pubmed:affiliationClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.lld:pubmed
pubmed-article:1987288pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:1987288pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed