{
  "abstract": "During respiratory virus infections, CD8⁺ T cells kill virus-infected cells and establish antigen-specific immune memory, but excessive or dysregulated responses can also contribute to lung immunopathology. The development and maintenance of optimal CD8⁺ T cell effector and memory responses depend on mitochondrial fitness, which can be compromised across multiple physiologic and pathologic conditions. However, how impaired mitochondrial fitness affect antiviral CD8⁺ T cell responses remains poorly understood. Here, we used a CD8⁺ T cell-specific TFAM-haploinsufficient mouse model to induce moderate mitochondrial stress without the severe mitochondrial dysfunction associated with complete TFAM loss, providing a genetically controlled model of mitochondrial perturbations relevant to physiologic conditions. TFAM insufficiency disrupted mitochondrial integrity and cellular bioenergetics and increased mitochondrial DNA and oxidative stress in CD8⁺ T cells. During primary influenza A virus (IAV) infection, TFAM-insufficient CD8⁺ T cells exhibited heightened cytotoxic activity and inflammatory responses associated with lung immunopathology, followed by progressive functional exhaustion, diminished antigen-specific responses, and impaired protective immunity. Consistent with the physiologic relevance of these findings, CD8⁺ T cells from older individuals exhibited reduced TFAM expression and mitochondrial function. Collectively, our findings demonstrate that moderate mitochondrial stress can alter the trajectory of antiviral CD8⁺ T cell responses, promoting pathogenic effector activity during acute infection while compromising subsequent protective immunity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Zahrasadat Navaeiseddighi"
    },
    {
      "name": "Kai Guo"
    },
    {
      "name": "Syed Shafat Hasan"
    },
    {
      "name": "Zhihan Wang"
    },
    {
      "name": "Rutuparnna Mishra"
    },
    {
      "name": "Taylor Schmit"
    },
    {
      "name": "Jamanah Ahsan"
    },
    {
      "name": "Emily J Moser"
    },
    {
      "name": "Junguk Hur"
    },
    {
      "name": "Jacob S. Yount"
    },
    {
      "name": "Ramkumar Mathur"
    },
    {
      "name": "Liang Zhou"
    },
    {
      "name": "Nadeem Khan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ee2mjrjgwb419.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754254",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13622243/",
  "id": "ee2mjrjgwb419",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://doi.org/10.64898/2026.09.24.754254",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7214552231",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754254v1.full.pdf",
  "pmcid": "PMC13622243",
  "pmid": "42818300",
  "published": "2026-09-24",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/ee2mjrjgwb419.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "PMC13622243",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.09.24.754254"
    },
    {
      "first_seen": "2026-10-30T12:24:43Z",
      "native_id": "10.64898/2026.09.24.754254",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754254v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "TFAM Dependent Mitochondrial Fitness Limits CD8⁺ T Cell Immunopathology and Sustains Protective Immunity during Viral Pneumonia",
  "title_text": "TFAM Dependent Mitochondrial Fitness Limits CD8⁺ T Cell Immunopathology and Sustains Protective Immunity during Viral Pneumonia",
  "type": "preprint",
  "updated_at": "2026-10-30T12:33:29Z",
  "url": "https://research.draconitic.com/paper/ee2mjrjgwb419",
  "venue": "bioRxiv",
  "versions": []
}