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
- 1Medical Faculty, Division of Molecular Hematology, Department of Laboratory Medicine, Lund University
- 2Medical Faculty, Wallenberg Center for Molecular Medicine and Lund Stem Cell Center, Lund University
- 3Childhood Cancer Centre, Skåne University Hospital
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.
Methods: 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.
Results: 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.
Discussion: 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.
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BibTeX
@article{hidalgo2026haploidentical,
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}},
author = {Isabel Hidalgo and Maria Björklund and Cornelis Jan Pronk},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1960755},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960755/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Isabel Hidalgo
AU - Maria Björklund
AU - Cornelis Jan Pronk
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1960755
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960755/full
AB - 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. Methods: 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. Results: 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. Discussion: 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.
SN - 1664-3224
ER -