{
  "abstract": "A new human xeno-free T cell expansion strategy enabled T cell receptor α/β (TCRα/β)-driven autologous reactivity and continuous long-term IL-2-dependent expansion of an unconventional professional T cell antigen-presenting cell (T-APC) subset. Autologous T-APC cultures were obtained from small peripheral blood mononuclear cell samples that yielded over 1020-fold expansions by an approach that did not require cell purification or genetic manipulation. Primary T-APCs constitutively expressed major histocompatibility complex class II glycoproteins, costimulatory B7 molecules, and FOXP3 in long-term culture. Autologous expansion yielded both CD4+ and CD8+ T-APC subsets that expressed signature activation markers and rapid cell division over 1 to 2 mo of culture in the absence of exogenous mitogenic or antigenic stimuli. Autologous IL-2-driven expansion of CD4+ T-APCs required TCR engagement because continuous T cell proliferation was blocked by neutralizing monoclonal antibodies against CD4, and constitutive expression of CD40L was inhibited by neutralizing major histocompatibility complex class II monoclonal antibodies. Long-term expansion required continuous TGF-β exposure, which increased HLA-DR and CD25 expression with consequent enhancement of antigen presentation, autologous TCR recognition, and IL-2 responsiveness. Low IL-2/TGF-β concentrations favored CD25high CD69low PD1low T-APC subsets, whereas high IL-2/TGF-β concentrations favored CD25low CD69high PD1high T-APC subsets. T-APC presentation of agonistic self-antigens induced extensive blastogenesis of polyclonal syngeneic responder T cells, some of which differentiated de novo into exponentially expanding T-APC lines. Overall, this study reveals professional T-APC subsets that exhibit exponential autologous expansion in vitro via autologous self-presentation and agonistic TCR self-recognition. These T-APCs may regulate homeostatic self-reactivity of the human TCRα/β repertoire and may mediate, in part, autologous mixed lymphocyte reactions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Christian K Smallwood",
      "orcid": "0009-0002-1525-214X"
    },
    {
      "affs": [
        0
      ],
      "name": "Sunny L Sneed",
      "orcid": "0000-0002-5683-2151"
    },
    {
      "affs": [
        0
      ],
      "name": "Chandler L Williford"
    },
    {
      "affs": [
        0
      ],
      "name": "Tylar S Roof"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark D Mannie",
      "orcid": "0000-0003-0475-8516"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1x8qepnwfh7cs.bib",
  "cited_by": 0,
  "doi": "10.1093/jimmun/vkag274",
  "fulltext_url": "https://europepmc.org/articles/PMC13686443",
  "id": "1x8qepnwfh7cs",
  "issns": [
    "0022-1767",
    "1550-6606"
  ],
  "landing_url": "https://europepmc.org/article/MED/42906129",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7223084768",
  "pdf_url": "https://europepmc.org/articles/PMC13686443?pdf=render",
  "pmcid": "PMC13686443",
  "pmid": "42906129",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1x8qepnwfh7cs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42906129",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42906129"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion.",
  "title_text": "A human self-stimulatory CD4+ T cell antigen-presenting cell subset presents and recognizes agonistic self-antigens to sustain exponential autologous clonal expansion.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/1x8qepnwfh7cs",
  "venue": "Journal of immunology (Baltimore, Md. : 1950)",
  "versions": []
}