{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:31:14Z","timestamp":1790289074857,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"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":[[2006,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Wiskott-Aldrich syndrome (WAS) protein (WASP) plays a key role in TCR-mediated activation and immunological synapse formation. However, the effects of WASP deficiency on effector functions of human CD4+ and CD8+ T cells remain to be determined. In this study, we report that TCR\/CD28-driven proliferation and secretion of IL-2, IFN-\u03b3, and TNF-\u03b1 are strongly reduced in CD8+ T cells from WAS patients, compared with healthy donor CD8+ T cells. Furthermore, WAS CD4+ T cells secrete low levels of IL-2 and fail to produce IFN-\u03b3 and TNF-\u03b1, while the production of IL-4, IL-5, and IL-10 is only minimally affected. Defective IL-2 and IFN-\u03b3 production persists after culture of naive WAS CD4+ T cells in Th1-polarizing conditions. The defect in Th1 cytokine production by WAS CD4+ and CD8+ T cells is also present at the transcriptional level, as shown by reduced IL-2 and IFN-\u03b3 mRNA transcripts after TCR\/CD28 triggering. The reduced transcription of Th1 cytokine genes in WAS CD4+ T cells is associated with a defective induction of T-bet mRNA and a reduction in the early nuclear recruitment of NFAT-1, while the defective activation of WAS CD8+ T cells correlates with reduced nuclear recruitment of both NFAT-1 and NFAT-2. Together, our data indicate that WASP regulates the transcriptional activation of T cells and is required specifically for Th1 cytokine production.<\/jats:p>","DOI":"10.4049\/jimmunol.177.10.7451","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:39:04Z","timestamp":1397849944000},"page":"7451-7461","source":"Crossref","is-referenced-by-count":100,"title":["Defective Th1 Cytokine Gene Transcription in CD4+ and CD8+ T Cells from Wiskott-Aldrich Syndrome Patients"],"prefix":"10.1093","volume":"177","author":[{"given":"Sara","family":"Trifari","sequence":"first","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Sitia","sequence":"additional","affiliation":[{"name":"Immunopathogenesis of Liver Infections Unit, San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Aiuti","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Scaramuzza","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marangoni","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele University , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca G","family":"Guidotti","sequence":"additional","affiliation":[{"name":"Immunopathogenesis of Liver Infections Unit, San Raffaele Scientific Institute , Milan ,","place":["Italy"]},{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin , Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Saracco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Turin , Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi D","family":"Notarangelo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Brescia, Spedali Civili , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Grazia","family":"Roncarolo","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele University , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loi\u0308c","family":"Dupre\u0301","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,11,15]]},"reference":[{"key":"2025032704311186300_R1","first-page":"3454","volume-title":"Blood","year":"2004"},{"key":"2025032704311186300_R2","first-page":"585","volume-title":"Curr. 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