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These pMHCII\u2010NPs that display epitopes from mitochondrial protein can blunt the progression of both autoimmune hepatitis (AIH) and experimental autoimmune encephalomyelitis (EAE) in mice carrying either disease. However, with co\u2010morbid mice having both diseases, these pMHCII\u2010NPs selectively treat AIH. In contrast, pMHCII\u2010NPs displaying central nervous system (CNS)\u2010specific epitopes can efficiently treat CNS autoimmunity, both in the absence and presence of AIH, without having any effects on the progression of the latter. Here, we develop a compartmentalized population model of T\u2010cells in co\u2010morbid mice to identify the mechanisms by which Tr1 cells mediate organ\u2010specific immunoregulation. We perform time\u2010series simulations and bifurcation analyses to study how varying physiological parameters, including local cognate antigenic load and rates of Tr1\u2010cell recruitment and retention, affect T\u2010cell allocation and Tr1\u2010mediated immunoregulation. Various regimes of behaviour, including \u2018competitive autoimmunity\u2019 where pMHCII\u2010NP\u2010treatment fails against both diseases, are identified and compared with experimental observations. Our results reveal that a transient delay in Tr1\u2010cell recruitment to the CNS, resulting from inflammation\u2010dependent Tr1\u2010cell allocation, accounts for the liver\u2010centric effects of AIH\u2010specific pMHCII\u2010NPs in co\u2010morbid mice as compared with mice exclusively having EAE. They also suggest that cognate autoantigen expression and local Tr1\u2010cell retention are key determinants of effective regulatory\u2010cell function. These results thus provide new insights into the rules that govern Tr1\u2010cell recruitment and their autoregulatory function.<\/jats:p>","DOI":"10.1111\/imm.13241","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T19:04:38Z","timestamp":1595271878000},"page":"209-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quantifying immunoregulation by autoantigen\u2010specific T\u2010regulatory type 1 cells in mice with simultaneous hepatic and extra\u2010hepatic autoimmune disorders"],"prefix":"10.1111","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-492X","authenticated-orcid":false,"given":"Hassan","family":"Jamaleddine","sequence":"first","affiliation":[{"name":"Department of Physiology McGill University Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pere","family":"Santamaria","sequence":"additional","affiliation":[{"name":"Department of Microbiology Immunology &amp; Infectious Diseases University of Calgary Calgary AL Canada"},{"name":"Institut D\u2019Investigacions Biom\u00e8diques August Pi i Sunyer Carrer del Rossell\u00f3, Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-9914","authenticated-orcid":false,"given":"Anmar","family":"Khadra","sequence":"additional","affiliation":[{"name":"Department of Physiology McGill University Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17300"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16962"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.04.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)00804-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.3.393"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1602864"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3179"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.493"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","unstructured":"PotC ApetohL KuchrooVK editors. 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