{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:33:43Z","timestamp":1791214423802,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"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":[[2000,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-12 plays a pivotal role in the stimulation of immune responses against intracellular infections. This role is manifested in the increased susceptibility to atypical mycobacterial and salmonella infections among individuals whose lymphocytes lack expression of IL-12R\u03b21. Here, we report on a patient with Mycobacterium avium infection, recurrent Staphylococcus aureus sinusitis, and multiple adverse drug reactions whose T cells were unable to produce IFN-\u03b3 or proliferate in response to IL-12 despite the expression of wild-type IL-12R\u03b21 and IL-12R\u03b22. The defect in these functional responses to IL-12 was selective, as cytolytic activity induced by IL-12 was intact, and lymphocytes were responsive to stimulation by IL-2. An examination of cytokine signaling revealed that STAT4 and extracellular regulated kinase 1 (ERK1) activation by IL-12 was intact, whereas the activation of STAT1, -3, and -5 by IL-12 was lost. This impairment of STAT activation was specific for IL-12, as STAT activation by IL-2, IL-15, and IFN-\u03b3 was unaffected. These findings demonstrate that the activation of STAT4 alone is not sufficient for IL-12-induced IFN-\u03b3 production and proliferation and suggest that other STATs play a role in these responses to IL-12. While the etiology of the impaired IL-12 signaling in this patient has not yet been elucidated, the absence of mutations in IL-12R\u03b21 or IL-12R\u03b22 and the preservation of STAT4 activation raise the possibility that there may be a mutation in an as yet undiscovered component of the IL-12 signaling complex that is normally required for the recruitment and activation of STAT1, -3, and -5.<\/jats:p>","DOI":"10.4049\/jimmunol.165.7.4120","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T02:25:30Z","timestamp":1398047130000},"page":"4120-4126","source":"Crossref","is-referenced-by-count":40,"title":["Impairment of STAT Activation by IL-12 in a Patient with Atypical Mycobacterial and Staphylococcal Infections"],"prefix":"10.1093","volume":"165","author":[{"given":"Jared A","family":"Gollob","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korina G","family":"Veenstra","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumi","family":"Jyonouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ferrieri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN 55455"},{"name":"Department of Laboratory Medicine\/Pathology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Panka","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fre\u0301de\u0301ric","family":"Altare","sequence":"additional","affiliation":[{"name":"Laboratoire de Ge\u0301ne\u0301tique Humaine des Maladies Infectieuses, Faculte\u0301 de Me\u0301decine Necker , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Fieschi","sequence":"additional","affiliation":[{"name":"Laboratoire de Ge\u0301ne\u0301tique Humaine des Maladies Infectieuses, Faculte\u0301 de Me\u0301decine Necker , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"Laboratoire de Ge\u0301ne\u0301tique Humaine des Maladies Infectieuses, Faculte\u0301 de Me\u0301decine Necker , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W","family":"Mier","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,10,1]]},"reference":[{"key":"2025032908050849800_R1","first-page":"251","volume-title":"Annu. 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