Table 1.
Examples of short-course regimens known to promote successful long-term acceptance of allogeneic or xenogeneic stem cells in mice. WBI = whole body irradiation; TI = thymic irradiation.
| Tolerance Regimen |
Treatment Course |
Mechanism of Action |
Findings | References |
|---|---|---|---|---|
| Indefinite survival of xenogeneic ES cells in testis but not in heart. | ||||
| CTLA4-Ig anti-CD40L anti-LFA1 |
6 to 8 days | Indefinite survival of xenogeneic ES and iPS cells, allogeneic ES and iPS cells in the leg muscle. | 82,110 | |
| CTLA4-Ig anti-CD40L 3Gy WBI |
2 days | Inhibits T cell activation by blocking CD28, CD40L, and LFA1 expressed on T cells. | Prolonged survival of xenogeneic ES cell-derived ECs and allogeneic iPS cell-derived NSCs. Permanent engraftment of fully MHC-mismatched allogeneic HSCs. Tolerance to donor skin. |
98,111 |
| Anti-CD40L 200cGy WBI |
14 days | Engraftment of fully MHC-mismatched HSCs. Long-term tolerance to donor skin. |
112 | |
| Non-depleting anti-CD8 & anti-CD4 |
4 days | Blocks CD8+ and CD4+ T cells from TCR-specific activation. Treg recruitment. |
Indefinite survival of allogeneic mouse ES cells and EBs. | 19,97 |
| Depleting anti-CD8 & anti-CD4 7Gy TI |
3 days | Depletes CD8+ and CD4+ T cells. | Permanent engraftment of fully MHC-mismatched allogeneic HSCs. Tolerance to donor skin. |
113 |