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Clarifying the mechanisms by which antigen-loaded nanoparticles establish tolerance is key to further adapting them to clinical use. The mechanisms underlying tolerance induction include the expansion of antigen-specific CD4+ regulatory T cells and sequestration of autoreactive cells in the spleen. In this study, we employed nanoparticles loaded with two model peptides, GP33\u201341 (a CD8 T cell epitope derived from lymphocytic choriomeningitis virus) and OVA323\u2013339 (a CD4 T cell epitope derived from ovalbumin), to modulate the CD8+ and CD4+ T cells from two transgenic mouse strains, P14 and DO11.10, respectively. Firstly, it was found that the injection of P14 mice with particles bearing the MHC I-restricted GP33\u201341 peptide resulted in the expansion of CD8+ T cells with a regulatory cell phenotype. This correlated with reduced CD4+ T cell viability in ex vivo co-cultures. Secondly, both nanoparticle types were able to sequester transgenic T cells in secondary lymphoid tissue. Flow cytometric analyses showed a reduction in the surface expression of chemokine receptors. Such an effect was more prominently observed in the CD4+ cells rather than the CD8+ cells.<\/jats:p>","DOI":"10.3390\/cells10123445","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T09:52:29Z","timestamp":1638870749000},"page":"3445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tolerance Induced by Antigen-Loaded PLG Nanoparticles Affects the Phenotype and Trafficking of Transgenic CD4+ and CD8+ T Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Tobias","family":"Neef","sequence":"first","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-2580","authenticated-orcid":false,"given":"Igal","family":"Ifergan","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Beddow","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Penaloza-MacMaster","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Haskins","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie D.","family":"Shea","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Podojil","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"},{"name":"Research & Development, Cour Pharmaceuticals Development Company, Northbrook, IL 60062, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9556-0718","authenticated-orcid":false,"given":"Stephen D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, School of Medicine, Northwestern University Feinberg, 303 E. Chicago Avenue, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s11892-017-0914-z","article-title":"Tolerogenic Nanoparticles to Treat Islet Autoimmunity","volume":"17","author":"Neef","year":"2017","journal-title":"Curr. 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