{
  "abstract": "CD4+ cytotoxic T lymphocytes (CD4-CTLs) are understudied immune mediators with ambiguous origins. Despite expressing RUNX3, granzyme B (GZMB), and perforin (PRF1), CD4-CTLs are frequently classified as Th1 extensions due to shared interferon-{gamma} (IFN{gamma}) and T-BET expression. Here, we identify interleukin-27 (IL-27) as a independent inducer of a distinct CD4-CTL program. Proteomics reveals that while IL-27-polarized CD4+ T cells share protein signatures with conventional Th1s and CD8+ T cells, they possess a unique molecular landscape with re-wired cytokine signaling networks and a potent cytotoxic protein profile. Mechanistically, this program requires STAT1 and T-BET but operates independently of the autocrine IFN{gamma} feedback that sustains Th1 cells. During acute murine cytomegalovirus infection, IL-27 receptor signaling contributes to CD4-CTL differentiation in vivo, as its loss leads to reduced GZMB expression and skews CD4+ T cells toward IFN{gamma}+ and FOXP3+ subsets. Together, these findings establish IL-27 as a potent and previously unappreciated inducer of CD4-CTLs.",
  "abstract_shown": true,
  "affiliations": [
    "La Jolla Institute for Immunlogy"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. I. Matias"
    },
    {
      "name": "R. Marrocco"
    },
    {
      "name": "K. Magro"
    },
    {
      "name": "L. D. Sanchez Solis"
    },
    {
      "name": "S. Figueroa Buezo"
    },
    {
      "name": "L. Laura Hinojosa-Gonzalez"
    },
    {
      "name": "M. Jabou"
    },
    {
      "name": "H. Lu"
    },
    {
      "name": "E. Ehinger"
    },
    {
      "name": "G. Ascui"
    },
    {
      "name": "Y. Zheng"
    },
    {
      "name": "F. AY"
    },
    {
      "name": "C. A. Benedict"
    },
    {
      "name": "S. A. Myers"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9rtamray3q3wk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.08.746061",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.746061v1.full",
  "id": "9rtamray3q3wk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.746061v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7213315443",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.08.746061v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9rtamray3q3wk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:26Z",
      "native_id": "10.64898/2026.09.08.746061",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.08.746061v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "IL-27 induces a cytotoxic state in CD4+ T cells distinct from the Th1 lineage",
  "title_text": "IL-27 induces a cytotoxic state in CD4+ T cells distinct from the Th1 lineage",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:26Z",
  "url": "https://research.draconitic.com/paper/9rtamray3q3wk",
  "venue": "bioRxiv",
  "versions": []
}