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Viable peripheral nerve allografts (PNAs) as growth\u2010guide conduits are immunologically rejected and all anucleated donor\/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation\u2010type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)\u2010fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated\/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG\u2010fused PNAs permanently restored many sciatic\u2010mediated behaviors within 2\u20136\u00a0weeks. PEG\u2010fused PNAs were not rejected even though host\/donors were neither immunosuppressed nor tissue\u2010matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG\u2010fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG\u2010fused PNAs exhibited attenuated innate and adaptive immune responses by 14\u201321\u00a0days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and\/or biochemically, PEG\u2010fused sciatic PNAs often resembled sciatic\n                    <jats:italic>autografts<\/jats:italic>\n                    or intact sciatic nerves. In brief, PEG\u2010fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune\u2010privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24720","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T03:20:42Z","timestamp":1600658442000},"page":"2468-2495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Polyethylene glycol\u2010fusion repair of sciatic allografts in female rats achieves immunotolerance via attenuated innate and adaptive responses"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-0880","authenticated-orcid":false,"given":"Tyler A.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences University of Texas at Austin Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-1186","authenticated-orcid":false,"given":"Cameron L.","family":"Ghergherehchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of Texas at Austin Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Mikesh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimie T.","family":"Shores","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Vascularized Composite Allotransplantation (VCA) Laboratory Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley O.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of Texas at Austin Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5610-6264","authenticated-orcid":false,"given":"George D.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13242"},{"issue":"4","key":"e_1_2_11_3_1","first-page":"561","article-title":"Identification of CD68(+) neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease","volume":"6","author":"Amanzada A.","year":"2013","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(90)90058-U"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0b013e31823f000e"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25894"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23023"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.224363"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23685"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.5625\/lar.2015.31.4.166"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamafacial.2018.0308"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780195169904.001.0001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.164"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.03.018"},{"key":"e_1_2_11_15_1","first-page":"611","article-title":"Quantitative integrated muscle function following reinnervation","volume":"37","author":"Carlton J. 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