{
  "abstract": "Introduction: Immune reconstitution following HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) is often delayed compared with HLA-identical transplantation, which frequently poses clinical challenges. The reasons for these differences in reconstitution kinetics remain poorly understood, and direct comparisons between the two settings are difficult to perform in the clinic.\n\nMethods: We therefore generated a mouse model of Haplo-HCT by crossing C57B6 and BALB/c mice to obtain C6BF1 offspring, and transplanted equal numbers of T- and B-cell-depleted bone marrow cells from either C6BF1 (haploidentical) or C57B6xB6SJL (identical, syngeneic) donors into conditioned, immunodeficient Rag1-deficient recipients that cannot generate autologous mature B or T cells. Immune reconstitution was monitored every 2-4 weeks by blood and immune-cell counts, immunoglobulin production, and T- and B-cell rearrangement activity (TREC/KREC), and the response to viral inflammation was assessed by poly(I:C) injections, with mice analyzed up to 16 weeks after transplantation.\n\nResults: Haploidentically transplanted mice showed higher early chimerism of myeloid and NK cells than identically transplanted mice at 8 weeks, with chimerism no longer significantly different by 16 weeks. Overall B- and T-cell production showed no significant differences between the two groups (apart from a tendency toward lower CD8 T-cell numbers in the haploidentical setting), immunoglobulin recovery was faster after Haplo-HCT, and TREC recovery kinetics showed no significant differences. Inflammatory responses to poly(I:C) showed no significant differences between the two settings in both settings. Overall, Haplo-HCT reconstitution was not found to be inferior to MHC-identical HCT in this model, with several parameters favouring the haploidentical setting, and the higher early chimerism may reflect superior replenishment of haploidentical myeloid and NK cells or cytotoxic activity of haploidentical T cells against residual host cells.\n\nDiscussion: These findings indicate that haploidentical grafts are not intrinsically inferior for immune reconstitution in this model and suggest that the delayed reconstitution observed clinically after Haplo-HCT more likely reflects differences in conditioning and graft manipulation than the haploidentical nature of the transplanted cells.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Faculty, Division of Molecular Hematology, Department of Laboratory Medicine, Lund University",
    "Medical Faculty, Wallenberg Center for Molecular Medicine and Lund Stem Cell Center, Lund University",
    "Childhood Cancer Centre, Skåne University Hospital"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Isabel Hidalgo"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Björklund"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Cornelis Jan Pronk"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1m7kxag0g52c5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1960755",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735720/",
  "id": "1m7kxag0g52c5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960755/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2720|Hematopoietic Stem Cell Transplantation"
    ]
  ],
  "openalex": "W7223187135",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1960755/pdf",
  "pmcid": "PMC13735720",
  "pmid": "42991297",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1m7kxag0g52c5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1960755",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960755/full"
    },
    {
      "first_seen": "2026-11-09T12:21:21Z",
      "native_id": "PMC13735720",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1960755"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Haploidentical and MHC-identical cells exhibit broadly similar immune reconstitution kinetics, with some compartment-specific differences, following hematopoietic cell transplantation in a murine model of severe combined immunodeficiency",
  "title_text": "Haploidentical and MHC-identical cells exhibit broadly similar immune reconstitution kinetics, with some compartment-specific differences, following hematopoietic cell transplantation in a murine model of severe combined immunodeficiency",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:21Z",
  "url": "https://research.draconitic.com/paper/1m7kxag0g52c5",
  "venue": "Frontiers in Immunology",
  "versions": []
}