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Due to the lack of a consensus on the phenotype of regulatory CD8+ T cells and very low frequency in the body, its clinical use as adoptive cellular therapy has not advanced much. In the present work, using DNA methyltransferase inhibitor 5-Aza-2\u2032-deoxycytidine (Aza), we efficiently and stably differentiated na\u00efve CD8+ T cells (CD8+CD25\u2013CD44\u2013 cells) into the CD8+Foxp3+ regulatory CD8+ T cells (CD8 Tregs). We also generated OVA peptide257-264-specific CD8+Foxp3+ Tregs. Compared with activated CD8 T cells, Aza plus TGF-\u03b2-induced CD8+Foxp3+ Tregs showed significantly increased surface expression of CD39, CD73, CD122, CD62L, and CD103, and secreted TGF-\u03b2\u00a0and suppressed the proliferation of effector CD4+ T cells. Interestingly, CD8+Foxp3+ Tregs exhibited low expression of perforin and granzyme required for cytotoxic function. Analysis of chemokine receptors showed that TGF-\u03b2\u00a0+\u00a0Aza induced CD8+Foxp3+ Tregs expressed gut-tropic chemokine receptors CCR6 and CCR9, and chemokine receptors CCR7 and CXCR3 required for mobilization into the spleen, lymph nodes, and gut-associated lymphoid tissues. Adoptive transfer of induced CD8+Foxp3+ Tregs restored cholera toxin-induced breakdown of oral tolerance to OVA by regulating OVA-specific IgE and IgG1. Altogether, we showed an efficient method to generate antigen-specific CD8+Foxp3+ Tregs, and the adoptive transfer of these cells induces oral tolerance by suppressing allergic response and maintaining intestinal homeostasis.<\/jats:p>","DOI":"10.1002\/jlb.5a0122-027r","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T08:08:57Z","timestamp":1661328537000},"page":"1497-1507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In vitro-induced Foxp3+CD8+ regulatory T cells suppress allergic IgE response in the gut"],"prefix":"10.1093","volume":"112","author":[{"given":"Shilpi","family":"Giri","sequence":"first","affiliation":[{"name":"National Centre for Cell Science, NCCS Complex , Ganeshkhind, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heikrujam Thoihen","family":"Meitei","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, NCCS Complex , Ganeshkhind, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandip Ashok","family":"Sonar","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, NCCS Complex , Ganeshkhind, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saumitra","family":"Shaligram","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, NCCS Complex , Ganeshkhind, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girdhari","family":"Lal","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, NCCS Complex , Ganeshkhind, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"issue":"11","key":"2023032107473937900_","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20112810","article-title":"The evolving role of CD8(+)CD28(-) immunosenescent T 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