{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:49:26Z","timestamp":1789872566975,"version":"4.0.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Activation of naive CD8 T cells in vitro in the presence of IL-4 induces type 2 cytokine expression, loss of CD8 expression, and reduced cytolytic potential. This represents a major shift from the canonical phenotype of effector CD8 T cells. It has not been established, however, whether IL-4 can induce comprehensive type 2 cytokine expression by CD8 T cells in vivo, nor whether the effects of IL-4 on type 2 cytokine production by CD8 T cells can be inhibited by IFN-\u03b3. Furthermore, disparate results have been reported regarding the anti-tumor ability of type 2 polarized effector CD8 T cells, and the effects of IFN-\u03b3 in this respect remain unknown. To address these questions, wild-type or IFN-\u03b3\u2013deficient OVA-specific CD8+ T cells were activated in RAG-2\u2212\/\u2212 \u03b3c\u2212\/\u2212 recipients with control or IL-4\u2013expressing OVA+ tumor cells, and then transferred to secondary recipients for tumor challenge. Tumor-derived IL-4 induced the expression of type 2 cytokines and the transcription factor GATA-3 by responding CD8 T cells while reducing their CD8 coreceptor expression and ability to eliminate a secondary tumor challenge. Each of these effects of IL-4 was exaggerated in IFN-\u03b3\u2013deficient, compared with wild-type, CD8 T cells. The results demonstrate that endogenous IFN-\u03b3 counteracts the induction of type 2 cytokines and the downregulation of both CD8 coreceptor levels and the anti-tumor response in CD8 T cells exposed to IL-4 during activation in vivo. These findings may explain the anomalies in the reported functional phenotype of type 2 polarized CD8 T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.0903372","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T05:37:08Z","timestamp":1277098628000},"page":"998-1004","source":"Crossref","is-referenced-by-count":29,"title":["IFN-\u03b3 Inhibits IL-4\u2013Induced Type 2 Cytokine Expression by CD8 T Cells In Vivo and Modulates the Anti-Tumor Response"],"prefix":"10.1093","volume":"185","author":[{"given":"Simon H","family":"Apte","sequence":"first","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Groves","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Olver","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Baz","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise L","family":"Doolan","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kelso","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Kienzle","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Brisbane, Queensland ,","place":["Australia"]},{"name":"Cooperative Research Centre for Vaccine Technology , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"2025032411404532900_r1","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1189\/jlb.0906583","article-title":"IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells","volume":"81","author":"Acacia de Sa Pinheiro","year":"2007","journal-title":"J. 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