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Among these, Th17 cells play an important role in promoting inflammatory damage to the myelin sheath and disrupting the integrity of blood brain barrier fibres. Despite advances in immunotherapy, there is no vaccine or durable cure for the disease. Regulatory T cells (Tregs) play a protective role against Th17\u2010mediated damage of myelin sheath. In this study, we investigated whether rapamycin, a well\u2010characterized mTOR inhibitor known to favour differentiation and metabolic reprogramming of Tregs, could synergize with MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    \u2010peptide to convert na\u00efve T cells into protective, MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    \u2010specific Tregs. To test this, mice were immunized with a combination of NOAEL (No Observed Adverse Effect Level) dose of MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    and rapamycin. Remarkably, upon subsequent challenge with a disease\u2010inducing (morbific) dose of MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    , the immunized animals showed pronounced resistance to clinical symptoms of experimental autoimmune encephalomyelitis (EAE). While the unimmunized group showed severe EAE symptoms. Notably, there was a significant increase in the population of memory Tregs that primarily expressed an immunosuppressive phenotype (FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    , TGF\u2010\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    , IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    ). This was accompanied by a decline in Th17 cells. Additionally, a substantial increase in the pool of myeloid\u2010derived suppressor cells (MDSCs) was observed in the rapamycin treated group, further contributing immunoregulatroy landscape. The underlying mechanism of this phenomenon was associated with the modulation of autophagic pathways by rapamycin, encouraging the differentiation of na\u00efve CD4 T cells into MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    \u2010specific Tregs, as evidenced by tetramer staining. These findings provide a conceptual framework for exploring strategies aimed at promoting antigen\u2010specific tolerance in autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1111\/imm.70158","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:20:24Z","timestamp":1781576424000},"page":"118-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MOG<\/scp>\n                    \u2010Peptide Synergizes With Rapamycin to Drive\n                    <scp>CD4<\/scp>\n                    <sup>+<\/sup>\n                    T Cells Into Protective Antigen\u2010Specific Tregs in\n                    <scp>EAE<\/scp>"],"prefix":"10.1111","volume":"179","author":[{"given":"Mohammad Adeel","family":"Zafar","sequence":"first","affiliation":[{"name":"Immunology Laboratory, Department of Biomedical Engineering Indian Institute of Technology Ropar  Rupnagar 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Ahmad","family":"Malik","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Department of Biomedical Engineering Indian Institute of Technology Ropar  Rupnagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-8642","authenticated-orcid":false,"given":"Mehdi","family":"Benamar","sequence":"additional","affiliation":[{"name":"Division of Immunology Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis\u2010Marie","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"Division of Immunology Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts 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