{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:46Z","timestamp":1787030866309,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI106791"],"award-info":[{"award-number":["R01 AI106791"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AI35296"],"award-info":[{"award-number":["P01 AI35296"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI007313"],"award-info":[{"award-number":["T32 AI007313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Minnesota Partnership for Biotechnology and Medical Genomics","award":["MNP#18.01"],"award-info":[{"award-number":["MNP#18.01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Optimal ex vivo expansion protocols of tumor-specific T cells followed by adoptive cell therapy must yield T cells able to home to tumors and effectively kill them. Our previous study demonstrated ex vivo activation in the presence of IL-12\u2013induced optimal CD8+ T cell expansion and melanoma regression; however, adverse side effects, including autoimmunity, can occur. This may be due to transfer of high-avidity self-specific T cells. In this study, we compared mouse low- and high-avidity T cells targeting the tumor Ag tyrosinase-related protein 2 (TRP2). Not surprisingly, high-avidity T cells provide superior tumor control, yet low-avidity T cells can promote tumor regression. The addition of IL-12 during in vitro expansion boosts low-avidity T cell responsiveness, tumor regression, and prevents T cell exhaustion. In this study, we demonstrate that IL-12\u2013primed T cells are resistant to PD-1\/PD-L1\u2013mediated suppression and retain effector function. Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while simultaneously increasing KLRG1. Using intravital imaging, we also determined that high-avidity T cells have sustained contacts with intratumoral dendritic cells and tumor targets compared with low-avidity T cells. However, with Ag overexpression, this defect is overcome, and low-avidity T cells control tumor growth. Taken together, these data illustrate that low-avidity T cells can be therapeutically beneficial if cocultured with IL-12 cytokine during in vitro expansion and highly effective in vivo if Ag is not limiting. Clinically, low-avidity T cells provide a safer alternative to high-avidity, TCR-engineered T cells, as IL-12\u2013primed, low-avidity T cells cause less autoimmune vitiligo.<\/jats:p>","DOI":"10.4049\/jimmunol.2000007","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T15:18:11Z","timestamp":1596208691000},"page":"1449-1460","source":"Crossref","is-referenced-by-count":37,"title":["Adoptive T Cell Therapy with IL-12\u2013Preconditioned Low-Avidity T Cells Prevents Exhaustion and Results in Enhanced T Cell Activation, Enhanced Tumor Clearance, and Decreased Risk for Autoimmunity"],"prefix":"10.1093","volume":"205","author":[{"given":"Christopher G","family":"Tucker","sequence":"first","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Martinov","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0922-7722","authenticated-orcid":false,"given":"Brandon J","family":"Burbach","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-3949","authenticated-orcid":false,"given":"Lalit K","family":"Beura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovejot M","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F","family":"Mescher","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-5637","authenticated-orcid":false,"given":"Brian T","family":"Fife","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2025030417504898300_r1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov."},{"key":"2025030417504898300_r2","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1001\/jamaoncol.2019.2187","article-title":"Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab","volume":"5","author":"Topalian","year":"2019","journal-title":"JAMA Oncol."},{"key":"2025030417504898300_r3","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"2025030417504898300_r4","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.aaf2807","article-title":"Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade","volume":"354","author":"Pauken","year":"2016","journal-title":"Science"},{"key":"2025030417504898300_r5","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1093\/annonc\/mdv383","article-title":"Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [Published erratum appears in 2016 Ann. Oncol. 27: 1362.]","volume":"26","author":"Naidoo","year":"2015","journal-title":"Ann. Oncol."},{"key":"2025030417504898300_r6","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1002\/cncr.30491","article-title":"Adoptive T cell therapy: an overview of obstacles and opportunities","volume":"123","author":"Baruch","year":"2017","journal-title":"Cancer"},{"key":"2025030417504898300_r7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/imr.12132","article-title":"Exploiting the curative potential of adoptive T-cell therapy for cancer","volume":"257","author":"Hinrichs","year":"2014","journal-title":"Immunol. Rev."},{"key":"2025030417504898300_r8","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1158\/1078-0432.CCR-10-0041","article-title":"Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients","volume":"16","author":"Besser","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"2025030417504898300_r9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/CJI.0b013e3182829903","article-title":"Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy","volume":"36","author":"Morgan","year":"2013","journal-title":"J. Immunother."},{"key":"2025030417504898300_r10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1053\/j.seminoncol.2012.01.006","article-title":"Advances in the treatment of metastatic melanoma: adoptive T-cell therapy","volume":"39","author":"Bernatchez","year":"2012","journal-title":"Semin. Oncol."},{"key":"2025030417504898300_r11","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"2025030417504898300_r12","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1182\/blood-2013-03-490565","article-title":"Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma","volume":"122","author":"Linette","year":"2013","journal-title":"Blood"},{"key":"2025030417504898300_r13","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.4049\/jimmunol.182.3.1351","article-title":"IL-12 enhances CTL synapse formation and induces self-reactivity","volume":"182","author":"Markiewicz","year":"2009","journal-title":"J. Immunol."},{"key":"2025030417504898300_r14","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4049\/jimmunol.160.2.643","article-title":"Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity","volume":"160","author":"Morgan","year":"1998","journal-title":"J. Immunol."},{"key":"2025030417504898300_r15","doi-asserted-by":"crossref","first-page":"6973","DOI":"10.1073\/pnas.1221609110","article-title":"T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy","volume":"110","author":"Zhong","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030417504898300_r16","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jamcollsurg.2011.12.034","article-title":"Ex vivo interleukin-12-priming during CD8(+) T cell activation dramatically improves adoptive T cell transfer antitumor efficacy in a lymphodepleted host","volume":"214","author":"Rubinstein","year":"2012","journal-title":"J. Am. Coll. Surg."},{"key":"2025030417504898300_r17","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.4049\/jimmunol.169.12.6842","article-title":"The roles of IL-12 in providing a third signal for clonal expansion of naive CD8 T cells","volume":"169","author":"Valenzuela","year":"2002","journal-title":"J. Immunol."},{"key":"2025030417504898300_r18","article-title":"Intra-tumoral production of IL18, but not IL12, by TCR-engineered T cells is non-toxic and counteracts immune evasion of solid tumors","volume":"7","author":"Kunert","year":"2017","journal-title":"OncoImmunology"},{"key":"2025030417504898300_r19","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jss.2013.06.045","article-title":"Local secretion of IL-12 augments the therapeutic impact of dendritic cell-tumor cell fusion vaccination","volume":"185","author":"Tan","year":"2013","journal-title":"J. Surg. Res."},{"key":"2025030417504898300_r20","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/cgt.2013.54","article-title":"Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines","volume":"20","author":"Miguel","year":"2013","journal-title":"Cancer Gene Ther."},{"key":"2025030417504898300_r21","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/mt.2010.313","article-title":"Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment","volume":"19","author":"Zhang","year":"2011","journal-title":"Mol. Ther."},{"key":"2025030417504898300_r22","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.4049\/jimmunol.1300652","article-title":"Cutting edge: IL-12 and type I IFN differentially program CD8 T cells for programmed death 1 re-expression levels and tumor control","volume":"191","author":"Gerner","year":"2013","journal-title":"J. Immunol."},{"key":"2025030417504898300_r23","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00262-012-1378-2","article-title":"Modulating the differentiation status of ex vivo-cultured anti-tumor T cells using cytokine cocktails","volume":"62","author":"Yang","year":"2013","journal-title":"Cancer Immunol. Immunother."},{"key":"2025030417504898300_r24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/CJI.0b013e31819144d7","article-title":"Melanoma progression despite infiltration by in vivo-primed TRP-2-specific T cells","volume":"32","author":"Singh","year":"2009","journal-title":"J. Immunother."},{"key":"2025030417504898300_r25","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.4049\/jimmunol.1401571","article-title":"CD4+ T cell help selectively enhances high-avidity tumor antigen-specific CD8+ T cells","volume":"195","author":"Zhu","year":"2015","journal-title":"J. Immunol."},{"key":"2025030417504898300_r26","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.4049\/jimmunol.171.10.5165","article-title":"CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine","volume":"171","author":"Curtsinger","year":"2003","journal-title":"J. Immunol."},{"key":"2025030417504898300_r27","first-page":"4702","article-title":"Treatment of intracranial tumors by systemic transfer of superantigen-activated tumor-draining lymph node T cells","volume":"56","author":"Inoue","year":"1996","journal-title":"Cancer Res."},{"key":"2025030417504898300_r28","article-title":"Tumor vascular morphology undergoes dramatic changes during outgrowth of B16 melanoma while proangiogenic gene expression remains unchanged","volume":"2011","author":"Langenkamp","year":"2011","journal-title":"ISRN Oncol."},{"key":"2025030417504898300_r29","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1229620","article-title":"Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection","volume":"338","author":"Paley","year":"2012","journal-title":"Science"},{"key":"2025030417504898300_r30","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/ni.1790","article-title":"Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal","volume":"10","author":"Fife","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025030417504898300_r31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"2025030417504898300_r32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/ni.1679","article-title":"Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection","volume":"10","author":"Blackburn","year":"2009","journal-title":"Nat. Immunol."},{"key":"2025030417504898300_r33","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/ni.2046","article-title":"Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection","volume":"12","author":"Kao","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025030417504898300_r34","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.4049\/jimmunol.181.7.4832","article-title":"NFATc1 regulates PD-1 expression upon T cell activation","volume":"181","author":"Oestreich","year":"2008","journal-title":"J. Immunol."},{"key":"2025030417504898300_r35","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.immuni.2011.06.015","article-title":"Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8(+) T cells","volume":"35","author":"Youngblood","year":"2011","journal-title":"Immunity"},{"key":"2025030417504898300_r36","first-page":"937","article-title":"Expression of the DNA-binding factor TOX promotes the encephalitogenic potential of microbe-induced autoreactive CD8 + T cells. [Published erratum appears in 2019 Immunity 50: 763.]","volume-title":"Immunity","author":"Page","year":"2018"},{"key":"2025030417504898300_r37","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.89289","article-title":"Tumor-infiltrating lymphocytes are dynamically desensitized to antigen but are maintained by homeostatic cytokine","volume":"1","author":"Boldajipour","year":"2016","journal-title":"JCI Insight"},{"key":"2025030417504898300_r38","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1158\/2326-6066.CIR-13-0047","article-title":"Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity","volume":"1","author":"Dougan","year":"2013","journal-title":"Cancer Immunol. Res."},{"key":"2025030417504898300_r39","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1600-0749.1995.tb00648.x","article-title":"The expression of tyrosinase, tyrosinase-related proteins 1 and 2 (TRP1 and TRP2), the silver protein, and a melanogenic inhibitor in human melanoma cells of differing melanogenic activities","volume":"8","author":"Kameyama","year":"1995","journal-title":"Pigment Cell Res."},{"key":"2025030417504898300_r40","first-page":"364","article-title":"Quantification of tyrosinase, TRP-1, and Trp-2 transcripts in human melanocytes by reverse transcriptase-competitive multiplex PCR--regulation by steroid hormones","volume":"110","author":"Kippenberger","year":"1998","journal-title":"J. Invest. Dermatol."},{"key":"2025030417504898300_r41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1600-0749.1996.tb00107.x","article-title":"Transcription of melanogenesis enzymes in melanocytes: dependence upon culture conditions and co-cultivation with keratinocytes","volume":"9","author":"Kippenberger","year":"1996","journal-title":"Pigment Cell Res."},{"key":"2025030417504898300_r42","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0002-9440(10)64871-7","article-title":"Interferon-gamma reduces melanosomal antigen expression and recognition of melanoma cells by cytotoxic T cells","volume":"160","author":"Le Poole","year":"2002","journal-title":"Am. J. Pathol."},{"key":"2025030417504898300_r43","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1158\/0008-5472.CAN-12-3781","article-title":"Aire deficiency promotes TRP-1-specific immune rejection of melanoma","volume":"73","author":"Zhu","year":"2013","journal-title":"Cancer Res."},{"key":"2025030417504898300_r44","first-page":"370","article-title":"Intratumoral injection of dendritic cells overexpressing interleukin-12 inhibits melanoma growth","volume":"42","author":"Yao","year":"2019","journal-title":"Oncol. Rep."},{"key":"2025030417504898300_r45","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00262-018-2280-3","article-title":"Ex vivo conditioning with IL-12 protects tumor-infiltrating CD8+ T cells from negative regulation by local IFN-\u03b3","volume":"68","author":"Lin","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"2025030417504898300_r46","first-page":"2541","article-title":"Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production","volume":"90","author":"Leonard","year":"1997","journal-title":"Blood"},{"key":"2025030417504898300_r47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1158\/1078-0432.CCR-18-1512","article-title":"First-in-human phase I trial of a tumor-targeted cytokine (NHS-IL12) in subjects with metastatic solid tumors","volume":"25","author":"Strauss","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"2025030417504898300_r48","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/9056173","article-title":"Prospects of IL-2 in cancer immunotherapy","volume":"2018","author":"Choudhry","year":"2018","journal-title":"BioMed Res. Int."},{"key":"2025030417504898300_r49","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.3389\/fimmu.2018.02905","article-title":"Anti-cancer therapies employing IL-2 cytokine tumor targeting: contribution of innate, adaptive and immunosuppressive cells in the anti-tumor efficacy","volume":"9","author":"Mortara","year":"2018","journal-title":"Front. Immunol."},{"key":"2025030417504898300_r50","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/CMR.0000000000000436","article-title":"Combination immunotherapies implementing adoptive T-cell transfer for advanced-stage melanoma","volume":"28","author":"Foley","year":"2018","journal-title":"Melanoma Res."},{"key":"2025030417504898300_r51","article-title":"Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells","volume":"8","author":"Alsaieedi","year":"2018","journal-title":"OncoImmunology"},{"key":"2025030417504898300_r52","first-page":"981","article-title":"Ocular and systemic autoimmunity after successful tumor-infiltrating lymphocyte immunotherapy for recurrent, metastatic melanoma","volume-title":"Ophthalmology","author":"Yeh","year":"2009"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/205\/5\/1449\/61879841\/ji2000007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/205\/5\/1449\/61879841\/ji2000007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T13:13:28Z","timestamp":1741094008000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/205\/5\/1449\/7930764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2000007","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,9,1]]}}}