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However, these immunological models rely on either self\u2010antigens or self\u2010dendritic cells for understanding of central tolerance, which have been discussed by Fuchs and Matzinger in response to Al\u2010Yassin. In an attempt to address some questions that these models are facing when it comes to understanding central tolerance, I propose that the goal of negative selection in the thymus is to eliminate defective T cells but not self\u2010reactive T cells. Therefore, any escape from negative selection could increase lymphopenia because of the depletion of defective na\u00efve T cells outside the thymus, as seen in the elderly.<\/jats:p>","DOI":"10.1111\/sji.13209","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T16:31:11Z","timestamp":1659544271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The adaptation model of immunity: Is the goal of central tolerance to eliminate defective T cells or self\u2010reactive T cells?"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-2953","authenticated-orcid":false,"given":"Masoud H.","family":"Manjili","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, VCU School of Medicine VCU Massey Cancer Center  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12652"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12660"},{"key":"e_1_2_5_4_1","first-page":"1723","article-title":"Neonatal tolerance revisited: turning on newborn T cells with dendritic cells","volume":"271","author":"Ridge JP","year":"1996","journal-title":"Science (United States)"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2001.00974.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90198-G"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/smim.2000.0230"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1707"},{"key":"e_1_2_5_9_1","first-page":"833","article-title":"Antigen presentation in the thymus for positive selection and central tolerance induction","volume":"9","author":"Klein L","year":"2009","journal-title":"Nat Rev"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/15200"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.844315"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03886"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.766698"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4199"},{"key":"e_1_2_5_15_1","first-page":"3788","article-title":"CD28 costimulation can promote T cell survival by enhancing the expression of Bcl\u2010xL. 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