{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:40:19Z","timestamp":1791042019362,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":[[2011,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IFN-\u03b3 and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-\u03b3 in shaping the effector CD4+ and CD8+ T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-\u03b3\u2212\/\u2212 mice during P. berghei ANKA infection. The expansion of splenic CD4+ and CD8+ T cells during P. berghei ANKA infection was unaffected by the absence of IFN-\u03b3, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-\u03b3\u2212\/\u2212 mice; however, the migration to, and accumulation of, effector CD4+ and CD8+ T cells in the lung, liver, and brain was altered in IFN-\u03b3\u2212\/\u2212 mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-\u03b3, suggesting that IFN-\u03b3 influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-\u03b3\u2013dependent environmental signals\u2014leading to T cell apoptosis\u2014rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-\u03b3 in modulating T cell function during P. berghei ANKA infection and reveals that IFN-\u03b3 is required for efficient contraction of the pool of activated T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1100241","type":"journal-article","created":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T11:41:52Z","timestamp":1314877312000},"page":"2885-2897","source":"Crossref","is-referenced-by-count":47,"title":["Heterogeneous and Tissue-Specific Regulation of Effector T Cell Responses by IFN-\u03b3 during <i>Plasmodium berghei<\/i> ANKA Infection"],"prefix":"10.1093","volume":"187","author":[{"given":"Ana","family":"Villegas-Mendez","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Brian","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]},{"name":"Department of Immunology and Molecular Pathology, University College London Medical School , London, W1T 4JF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Murungi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius C R","family":"Hafalla","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tovah N","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Greig","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor M","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin N","family":"Couper","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,15]]},"reference":[{"key":"2025032410333790500_r1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1017\/S0031182009991715","article-title":"Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease","volume":"137","author":"de Souza","year":"2010","journal-title":"Parasitology"},{"key":"2025032410333790500_r2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.pt.2010.03.002","article-title":"Neuropathogenesis of human and murine malaria","volume":"26","author":"Riley","year":"2010","journal-title":"Trends Parasitol."},{"key":"2025032410333790500_r3","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0","article-title":"Involvement of IFN-\u03b3 receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection","volume":"30","author":"Amani","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"2025032410333790500_r4","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1365-3024.2008.01053.x","article-title":"Control of pathogenic CD8+ T cell migration to the brain by IFN-\u03b3 during experimental cerebral malaria","volume":"30","author":"Belnoue","year":"2008","journal-title":"Parasite Immunol."},{"key":"2025032410333790500_r5","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.1073\/pnas.86.14.5572","article-title":"Monoclonal antibody against interferon \u03b3 can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor","volume":"86","author":"Grau","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410333790500_r6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.ijpara.2006.02.016","article-title":"Immunopathogenesis of cerebral malaria","volume":"36","author":"Hunt","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"2025032410333790500_r7","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/eji.200737906","article-title":"CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-\u03b3\u2013induced chemokines","volume":"38","author":"Van den Steen","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2025032410333790500_r8","doi-asserted-by":"crossref","first-page":"14509","DOI":"10.1073\/pnas.0806727105","article-title":"Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8\u03b1+ dendritic cells","volume":"105","author":"Lundie","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410333790500_r9","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.4049\/jimmunol.181.2.1420","article-title":"Malaria-specific and nonspecific activation of CD8+ T cells during blood stage of Plasmodium berghei infection","volume":"181","author":"Miyakoda","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410333790500_r10","doi-asserted-by":"crossref","first-page":"6033","DOI":"10.4049\/jimmunol.178.10.6033","article-title":"Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria","volume":"178","author":"deWalick","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410333790500_r11","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1073\/pnas.0801544105","article-title":"Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria","volume":"105","author":"Campanella","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410333790500_r12","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4049\/jimmunol.180.2.1217","article-title":"Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency","volume":"180","author":"Miu","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410333790500_r13","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.4049\/jimmunol.178.9.5779","article-title":"NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria","volume":"178","author":"Hansen","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410333790500_r14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ijpara.2006.02.007","article-title":"Pathogenic T cells in cerebral malaria","volume":"36","author":"R\u00e9nia","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"2025032410333790500_r15","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.4049\/jimmunol.1003955","article-title":"Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria","volume":"186","author":"Haque","year":"2011","journal-title":"J. Immunol."},{"key":"2025032410333790500_r16","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.4049\/jimmunol.1000944","article-title":"Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria","volume":"185","author":"Amante","year":"2010","journal-title":"J. Immunol."},{"key":"2025032410333790500_r17","doi-asserted-by":"crossref","first-page":"e18720","DOI":"10.1371\/journal.pone.0018720","article-title":"CD8+ T cells and IFN-\u03b3 mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria","volume":"6","author":"Claser","year":"2011","journal-title":"PLoS ONE"},{"key":"2025032410333790500_r18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ijpara.2005.12.005","article-title":"Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria","volume":"36","author":"Potter","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"2025032410333790500_r19","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/ni794","article-title":"T-bet is a STAT1-induced regulator of IL-12R expression in na\u00efve CD4+ T cells","volume":"3","author":"Afkarian","year":"2002","journal-title":"Nat. Immunol."},{"key":"2025032410333790500_r20","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.immuni.2009.03.013","article-title":"Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12","volume":"30","author":"Schulz","year":"2009","journal-title":"Immunity"},{"key":"2025032410333790500_r21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1084\/jem.194.2.165","article-title":"Interferon gamma stabilizes the T helper cell type 1 phenotype","volume":"194","author":"Zhang","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032410333790500_r22","doi-asserted-by":"crossref","first-page":"4671","DOI":"10.4049\/jimmunol.160.10.4671","article-title":"Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation","volume":"160","author":"Aloisi","year":"1998","journal-title":"J. Immunol."},{"key":"2025032410333790500_r23","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.175.9.5624","article-title":"Cutting edge: early IFN-\u03b3 signaling directly enhances primary antiviral CD4+ T cell responses","volume":"175","author":"Whitmire","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410333790500_r24","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1084\/jem.20041463","article-title":"Interferon-gamma acts directly on CD8+ T cells to increase their abundance during virus infection","volume":"201","author":"Whitmire","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032410333790500_r25","doi-asserted-by":"crossref","first-page":"693","DOI":"10.4049\/jimmunol.180.2.693","article-title":"Cutting edge: T-bet and IL-27R are critical for in vivo IFN-\u03b3 production by CD8 T cells during infection","volume":"180","author":"Mayer","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410333790500_r26","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1126\/science.290.5495.1354","article-title":"Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-\u03b3","volume":"290","author":"Badovinac","year":"2000","journal-title":"Science"},{"key":"2025032410333790500_r27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1084\/jem.192.1.117","article-title":"Interferon \u03b3 eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells","volume":"192","author":"Dalton","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025032410333790500_r28","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4049\/jimmunol.179.2.939","article-title":"IFN-\u03b3 acts directly on activated CD4+ T cells during mycobacterial infection to promote apoptosis by inducing components of the intracellular apoptosis machinery and by inducing extracellular proapoptotic signals","volume":"179","author":"Li","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410333790500_r29","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1128\/IAI.73.6.3577-3586.2005","article-title":"\u03b3 Interferon-induced T-cell loss in virulent Mycobacterium avium infection","volume":"73","author":"Fl\u00f3rido","year":"2005","journal-title":"Infect. Immun."},{"key":"2025032410333790500_r30","doi-asserted-by":"crossref","first-page":"7616","DOI":"10.4049\/jimmunol.178.12.7616","article-title":"Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-\u03b3 signaling","volume":"178","author":"Turner","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410333790500_r31","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1084\/jem.20011174","article-title":"The mechanism and significance of deletion of parasite-specific CD4+ T cells in malaria infection","volume":"195","author":"Xu","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032410333790500_r32","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1084\/jem.20020666","article-title":"Interferon \u03b3 is required for activation-induced death of T lymphocytes","volume":"196","author":"Refaeli","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032410333790500_r33","doi-asserted-by":"crossref","first-page":"842","DOI":"10.4049\/jimmunol.180.2.842","article-title":"IFN-\u03b3 mediates the death of Th1 cells in a paracrine manner","volume":"180","author":"Foulds","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410333790500_r34","doi-asserted-by":"crossref","first-page":"7710","DOI":"10.4049\/jimmunol.0901274","article-title":"IFN-\u03b3 expressed by T cells regulates the persistence of antigen presentation by limiting the survival of dendritic cells","volume":"183","author":"Russell","year":"2009","journal-title":"J. Immunol."},{"key":"2025032410333790500_r35","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.4049\/jimmunol.167.7.3903","article-title":"Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection","volume":"167","author":"Wipasa","year":"2001","journal-title":"J. Immunol."},{"key":"2025032410333790500_r36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1046\/j.1365-3024.2001.00422.x","article-title":"Mouse splenic CD4+ and CD8+ T cells undergo extensive apoptosis during a Plasmodium chabaudi chabaudi AS infection","volume":"23","author":"Sanchez-Torres","year":"2001","journal-title":"Parasite Immunol."},{"key":"2025032410333790500_r37","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/j.1365-3024.2008.01050.x","article-title":"Blood stage malaria antigens induce different activation-induced cell death programs in splenic CD4+ T cells","volume":"30","author":"Mukherjee","year":"2008","journal-title":"Parasite Immunol."},{"key":"2025032410333790500_r38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.immunol.23.021704.115638","article-title":"Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research","volume":"23","author":"Good","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2025032410333790500_r39","doi-asserted-by":"crossref","first-page":"6461","DOI":"10.4049\/jimmunol.1001343","article-title":"STAT1-activating cytokines limit Th17 responses through both T-bet\u2013dependent and \u2013independent mechanisms","volume":"185","author":"Villarino","year":"2010","journal-title":"J. Immunol."},{"key":"2025032410333790500_r40","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1046\/j.1365-3083.1998.00435.x","article-title":"Interleukin-4 and interferon-\u03b3: the quintessence of a mutual antagonistic relationship","volume":"48","author":"Paludan","year":"1998","journal-title":"Scand. J. Immunol."},{"key":"2025032410333790500_r41","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-\u03b3: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"2025032410333790500_r42","doi-asserted-by":"crossref","first-page":"e1000369","DOI":"10.1371\/journal.ppat.1000369","article-title":"IP-10\u2013mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection","volume":"5","author":"Nie","year":"2009","journal-title":"PLoS Pathog."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/6\/2885\/62478843\/1100241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/187\/6\/2885\/62478843\/1100241.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T03:49:47Z","timestamp":1743133787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/187\/6\/2885\/7974070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,9,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1100241","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,9]]},"published":{"date-parts":[[2011,9]]}}}