{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:56:21Z","timestamp":1789898181542,"version":"4.0.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Functional exhaustion of CD8<jats:sup>+<\/jats:sup>T cells due to increased expression of inhibitory molecule PD-1 (Programmed Death-1) causes reactivation of latent disease during later phases of chronic toxoplasmosis. Onset of disease recrudescence results in decreased parasite cyst burden concomitant with parasites undergoing stage conversion from a primarily encysted, quiescent bradyzoite to a fast-replicating, highly motile tachyzoite. Thus, reduced cyst burden is one of the early hallmarks of disease recrudescence. This was further validated by depleting gamma interferon (IFN-\u03b3), a cytokine known to control latent toxoplasmosis, in chronically infected prerecrudescent mice. Since CD8<jats:sup>+<\/jats:sup>T cells (an important source of IFN-\u03b3) lose their functionality during the later phases of chronic toxoplasmosis, we next examined if adoptive transfer of functional CD8<jats:sup>+<\/jats:sup>T cells from acutely infected donors to the chronically infected prerecrudescent hosts could impede parasite de-encystation and rescue exhausted CD8<jats:sup>+<\/jats:sup>T cells. While the transfer of immune CD8<jats:sup>+<\/jats:sup>T cells temporarily restricted the breakdown of cysts, the exhausted endogenous CD8<jats:sup>+<\/jats:sup>T cell population was not rescued. Over time, the donor population got deleted, resulting in parasite de-encystation and host mortality. Considering that donor CD8<jats:sup>+<\/jats:sup>T cells fail to become long-lived, one of the cardinal features of memory CD8<jats:sup>+<\/jats:sup>T cells, it bears the implication that memory CD8 differentiation is impaired during chronic toxoplasmosis. Moreover, our data strongly suggest that while adoptive immunotherapy can prevent parasite de-encystation transiently, reduced antigen burden in the chronic phase by itself is insufficient for rescue of exhausted CD8<jats:sup>+<\/jats:sup>T cells. The conclusions of this study have profound ramifications in designing immunotherapeutics against chronic toxoplasmosis.<\/jats:p>","DOI":"10.1128\/iai.00784-12","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T04:30:32Z","timestamp":1372739432000},"page":"3414-3425","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Donor CD8<sup>+<\/sup>T Cells Prevent Toxoplasma gondii De-Encystation but Fail To Rescue the Exhausted Endogenous CD8<sup>+<\/sup>T Cell Population"],"prefix":"10.1128","volume":"81","author":[{"given":"Rajarshi","family":"Bhadra","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin A.","family":"Cobb","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtiaz A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.09.27"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/344462"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199006000-00004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2217\/imt.11.68"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/243796"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000190"},{"key":"e_1_3_2_8_2","first-page":"1","article-title":"Surveillance for AIDS-defining opportunistic illnesses, 1992\u20131997","volume":"48","author":"Jones JL","year":"1999","unstructured":"JonesJLHansonDLDworkinMSAldertonDLFlemingPLKaplanJEWardJ. 1999. Surveillance for AIDS-defining opportunistic illnesses, 1992\u20131997. MMWR CDC Surveill. Summ. 48:1\u201322.","journal-title":"MMWR CDC Surveill. Summ."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/apc.2005.19.626"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2006.11.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.02.021"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601438103"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1504.081306"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1206.060025"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4049\/jimmunol.149.1.175","article-title":"Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii","volume":"149","author":"Gazzinelli R","year":"1992","unstructured":"GazzinelliRXuYHienySCheeverASherA. 1992. Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J. Immunol. 149:175\u2013180.","journal-title":"J. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.4049\/jimmunol.143.6.2045","article-title":"Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice","volume":"143","author":"Suzuki Y","year":"1989","unstructured":"SuzukiYConleyFKRemingtonJS. 1989. Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice. J. Immunol. 143:2045\u20132050.","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015298108"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102319"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis304"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002903"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbt006"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.4049\/jimmunol.157.5.2103","article-title":"IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice","volume":"157","author":"Khan IA","year":"1996","unstructured":"KhanIAKasperLH. 1996. IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice. J. Immunol. 157:2103\u20132108.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-08-0458"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2012.07.018"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(02)02248-1"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00734512"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.11.2.267"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4730"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00085-07"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0666"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2005.25.338"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01354-06"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0657"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1744"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070064"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.3.2400-2407.1997"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.4049\/jimmunol.140.11.3943","article-title":"Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice","volume":"140","author":"Suzuki Y","year":"1988","unstructured":"SuzukiYRemingtonJS. 1988. Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice. J. Immunol. 140:3943\u20133946.","journal-title":"J. Immunol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010842"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.628"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00297-10"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkf251"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139393"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090825"},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.4049\/jimmunol.162.6.3512","article-title":"Inhibition of inducible nitric oxide synthase exacerbates chronic cerebral toxoplasmosis in Toxoplasma gondii-susceptible C57BL\/6 mice but does not reactivate the latent disease in T. gondii-resistant BALB\/c mice","volume":"162","author":"Schl\u00fcter D","year":"1999","unstructured":"Schl\u00fcterDDeckert-SchluterMLorenzEMeyerTRollinghoffMBogdanC. 1999. Inhibition of inducible nitric oxide synthase exacerbates chronic cerebral toxoplasmosis in Toxoplasma gondii-susceptible C57BL\/6 mice but does not reactivate the latent disease in T. gondii-resistant BALB\/c mice. J. Immunol. 162:3512\u20133518.","journal-title":"J. Immunol."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03406.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809818106"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.06.014"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v31.i4.10"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002042"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.014"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00784-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00784-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,2]],"date-time":"2023-07-02T20:33:08Z","timestamp":1688329988000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00784-12"}},"subtitle":[],"editor":[{"given":"J. L.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1128\/IAI.00784-12"],"URL":"https:\/\/doi.org\/10.1128\/iai.00784-12","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9]]},"assertion":[{"value":"2012-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-08-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}