Alveolar bone resorption induced by CD4⁺CD45RB high-density T-cell transfer in immunocompromised mice

Background: The aims of this study are to determine whether the antigen-inexperienced (naive, CD45RB highdensity) T-cell (CD4 ⁺CD45RB^High T-cell) transfer model is associated with alveolar bone resorption, to elucidate the local osteogenic/adipogenic potential of alveolar bone marrow stromal cells (ABCs) from T-cell-transferred animals, and to investigate the systemic osteogenic potential by transplanting human periodontal ligament stem cells (hPDLSCs) into these animals. Methods: CD4 ⁺CD45RB^High and CD4⁺CD45RB^Low (antigenexperienced [memory, CD45RB low-density]) T cells were sorted and transferred into severe combined immunodeficiency (SCID) mice to induce inflammatory bowel disease- like syndrome (n = 8). hPDLSCs were transplanted into T-cell-transferred SCID mice to examine ectopic cementum formation 8 weeks after T-cell transfer. The mandibles and tibias of these mice were retrieved for microcomputed tomography (micro-CT), histomorphometric analysis, and isolation of ABCs 16 weeks after T-cell transfer. The in vitro osteogenic and adipogenic potentials of the ABCs were evaluated. Results: Histologic and micro-CT analysis revealed that the transfer of CD4⁺CD45RB^High T-cell subset was sufficient for alveolar bone resorption and affected the osteogenic/ adipogenic potential of ABCs. Furthermore, it was found that CD4 ⁺CD45RB^High T-cell-transferred animals have decreased systemic osteogenic potential, as evidenced using the in vivo ectopic hPDLSC transplantation model. Conclusion: CD4⁺CD45RB^High T-cell transfer induced both alveolar bone resorption and reduced systemic osteogenic potential, with a concomitant downregulation of the osteogenic potential of ABCs.