| First Author | Gross DA | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 6 | Pages | 1841-8 |
| PubMed ID | 16741251 | Mgi Jnum | J:138060 |
| Mgi Id | MGI:3804127 | Doi | 10.1182/blood-2006-02-011981 |
| Citation | Gross DA, et al. (2006) Simple conditioning with monospecific CD4+CD25+ regulatory T cells for bone marrow engraftment and tolerance to multiple gene products. Blood 108(6):1841-8 |
| abstractText | A major impediment to gene replacement therapy is immune elimination of genetically modified cells. In principle, this can be dealt with by inducing a strong, specific, and enduring tolerance through engraftment of transgene-modified autologous bone marrow (BM). Because usual myeloablation and/or immunosuppression are risk factors in most pathologies, we assessed the potential of monospecific CD4(+)CD25(+) regulatory T cells (Tregs) to engraft minor-mismatched BM without preconditioning. We found that as few as 5 x 10(4) Tregs directed to the male DBY protein promote the engraftment of foreign male BM into sex-mismatched female hosts, establishing sustained chimerism in all hematopoeitic compartments. We achieved concomitantly strong tolerance to all foreign antigens expressed in the BM, likely occurring through induction of anergy and/or deletion of antidonor T cells. Chimerism was obtained in thymectomized mice too, underlining the major role of peripheral tolerance mechanisms in our system. This allowed us to engraft gene-modified tissues while preserving full immunocompetence to third-party antigens. Our results demonstrate that very few donor-specific Tregs are effective as the sole conditioning to induce mixed molecular chimerism and long-term tolerance to multiple foreign antigens. |
