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Trajectory analysis showed that antigen-experienced effector memory T cells differentiated into suppressive Areg\n                    <jats:sup>+<\/jats:sup>\n                    Tr1 and EGFR\n                    <jats:sup>+<\/jats:sup>\n                    TOX\n                    <jats:sup>+<\/jats:sup>\n                    Nur77\n                    <jats:sup>+<\/jats:sup>\n                    TCF-1\n                    <jats:sup>\u2212<\/jats:sup>\n                    Tex subsets. Cell-cell communication mapping showed that exhausted and effector memory T cells engaged with allospecific Tr1 cells via the Areg-EGFR axis. Gene silencing studies confirmed that Tr1 cells use Areg-EGFR signaling to drive the metabolic suppression and epigenetic reprogramming of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells through a Nur77-dependent pathway. These findings point to the splenic Areg\n                    <jats:sup>+<\/jats:sup>\n                    Tr1 cell-EGFR\n                    <jats:sup>+<\/jats:sup>\n                    Teff cell axis as a critical immunoregulatory pathway in peripheral transplant tolerance.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea0567","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:58:36Z","timestamp":1767812316000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Allospecific splenic Tr1 cells drive effector T cell exhaustion through up-regulated Areg-EGFR signaling to promote transplant tolerance"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-1513","authenticated-orcid":true,"given":"Amar","family":"Singh","sequence":"first","affiliation":[{"name":"Schulze Diabetes Institute, Department of Surgery, University of Minnesota, 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