Table 2.
MDSC transfer for immune modulation or cell therapy of allograft rejection.
| Condition | Source of MDSC | Cell Dose and Route |
Model | Mechanism and Outcome | Reference |
|---|---|---|---|---|---|
| (i) No transplant | Tumor-bearing mouse splenocytes | 3–5×106i.v. 2–3d after T cell transfer | Ag-specific transgenic CD8+ T cell | Ag-specific CD8+ T cell tolerance but T cells remained responsive to non-specific αCD3 stimulation | (50) |
| Tumor-bearing mouse BM | 5×106 i.v. + 5µg/mouse peptide Ag d1 after T cell transfer | Transgenic T cell induction of diabetes | 75% diabetes-free at d30 (Ag-specific) with T cell anergy and induction of Treg | (64) | |
| Tumor-bearing mouse BM | 2×107 i.v. with T cells | NOD/SCID with transfer of diabetogenic T cells | 60% diabetes-free at d100 with reduced lymphocyte infiltration and insulitis | (64) | |
| (ii) Skin transplant | Transplant recipient splenocytes | 2×105 i.v. on d-1 and d3 | MHC class II-mismatched skin allograft | 50% long-term survival when transplant-activated MDSC transferred from ILT2 (HLA-G receptor) transgenic mice but not wild-type mice | (75) |
| Splenocytes from LPS-treated mice | 5×106 i.v. on d-1 | Male to female or MHC class II-mismatched skin allograft | Prolonged allograft survival dependent on heme oxygenase-1 | (80) | |
| (iii) Islet cell transplant | BALB/c BM cultures with GM-CSF+IL-6 or GM-CSF+G-CSF | 107 i.v. on d0, 7, 14 and 21 | Islet allograft (B6 to BALB/c) | Long-term survival in ~75% (GM-CSF+IL-6 MDSC) or ~40% (GM-CSF+G-CSF MDSC) without generalized immune suppression | (31) |
| B6 BM cultures with GM-CSF with liver stellate cells (B6, BALB/c or C3H) | 2.5×106 mixed with islets | Islet allograft (BALB/c to B6) | ~45–65% long-term survival, B7-H1-dependent increase in Treg that mediate T cell hyporesponsiveness | (163) | |
| (iv) GVHD | B6 BM cultures with GM-CSF+G-CSF+IL-13 | 2 or 6×106 i.v. with donor cells | GVHD (B6 to BALB/c) | Cell dose- and arginase-1-dependent improved survival with inhibition of CD4+ and CD8+ T cell responses and maintained graft-versus-leukemia effect | (32) |
| 129SvEv embryonic stem cell line cultured with KL, VEGF, Flt3L, TPO and M-CSF | 2×106 i.v. with donor cells, d4 and d10 | GVHD (129SvEv to BALB/c) | 82% long-term survival | (79) |
Abbreviations: G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte macrophage colony stimulating factor; ILT, immunoglobulin-like transcript; KL, c-Kit ligand; M-CSF, macrophage colony stimulating factor; NOD/SCID, non-obese diabetic/severe combined immune deficiency; VEGF, vascular endothelial growth factor; Flt3L, fms-like tyrosine kinase 3 ligand; TPO, thrombopoietin