Cd28 Activation Promotes Th2 Subset Differentiation by Human Cd4(+) Cells

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dc.contributor.authorKing, C. L.en
dc.contributor.authorStupi, R. J.en
dc.contributor.authorCraighead, N.en
dc.contributor.authorJune, C. H.en
dc.contributor.authorThyphronitis, G.en
dc.date.accessioned2015-11-24T16:35:12Z
dc.date.available2015-11-24T16:35:12Z
dc.identifier.issn0014-2980-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/7913
dc.rightsDefault Licence-
dc.subjectcd28en
dc.subjectth2en
dc.subjectinterleukin-4en
dc.subjecthuman cd4(+) cellsen
dc.subjectcd4+ t-cellsen
dc.subjectinterferon-gammaen
dc.subjectlymphocyte-ten
dc.subjectinterleukin-4en
dc.subjectcytokineen
dc.subjectclonesen
dc.subjectinductionen
dc.subjectresponsesen
dc.subjectil-4en
dc.subjectexpressionen
dc.titleCd28 Activation Promotes Th2 Subset Differentiation by Human Cd4(+) Cellsen
heal.abstractLigation of CD28 provides a costimulatory signal to T cells necessary for their activation resulting in increased interleukin (IL)-2 production in vitro, but its role in IL-4 and other cytokine production and functional differentiation of T helper (Th) cells remains uncertain. We studied the pattern of cytokine production by highly purified human adult and neonatal CD4(+) T cells activated with anti-CD3, phorbol 12-myristate 13-acetate (PMA) and ionomycin, or phytohemagglutinin (PHA) in the presence or absence of anti-CD28 in repetitive stimulation-rest cycles. Initial stimulation of CD4(+) cells with anti-CD3 (or the mitogens PHA or PMA+ionomycin) and anti-CD28 monoclonal antibodies induced IL-4, IL-5 and interferon-gamma (IFN-gamma) production and augmented IL-2 production (6- to 11-fold) compared to cells stimulated with anti-CD3 or mitogen alone. The anti-CD28-induced cytokine production corresponded with augmented IL-4 and IL-5 mRNA levels suggesting increased gene expression and/or mRNA stabilization. Most striking, however, was the progressively enhanced IL-4 and IL-5 production and diminished IL-2 and LFN-gamma production with repetitive consecutive cycles of CD28 stimulation. The enhanced Th2-like response correlated with an increased frequency of IL-4-secreting cells; up to 70 % of the cells produced IL-4 on the third round of stimulation compared to only 5 % after the first stimulation as determined by ELISPOT. CD28 activation also promoted a Th2 response in naive neonatal CD4(+) cells, indicating that Th cells are induced to express a Th2 response rather than preferential expansion of already established Th2-type cells. This CD28-mediated response was IL-4 independent, since enhanced IL-5 production with repetitive stimulation cycles was not affected in the presence of neutralizing anti-IL-4 antibodies. These results indicate that CD28 activation may play an important role in the differentiation of the Th2 subset in humans.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondary<Go to ISI>://A1995QY50600041-
heal.journalNameEur J Immunolen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate1995-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιώνel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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