Use of tolDC therapy to inhibit GVHD in mice
| TolDC . | GVHD model; treatment . | Effect on DCs (in vitro) . | Effect on GVHD . | Reference . |
|---|---|---|---|---|
| DC conditioning | ||||
| Rapamycin | MHC-mismatched (B6 → BALB/c) | MHC class II, CD80/CD86 expression ↓ | Survival ↑ | 117 |
| Host-type DCs day 0 | Intact in vivo trafficking | Histopathology ↓ | ||
| Intact CCR5, CCR7, and CD62L | ||||
| VIP | MHC (B6 → BALB/c, BALB/c → B6) and miHA-mismatched (B6 → F1) Host-type DCs day 2 and/or day 5 | Donor CD4+ T-cell Ag-specific response ↓ Induce Treg | Survival ↑ (miHA > MHA; early > late for MHA) | 118 146 |
| SAHA (HDAC inhibitor) | MHC-mismatched (BALB/c → B6) | CD40/CD80 expression ↓ | Survival ↑ | 104 |
| Host-type DCs days −1, 0, and 2 | TNF-α ↓ | |||
| T-cell proliferation ↓ | ||||
| TGF-β, IL-10 + LPS (DCreg)* | MHC-matched, miHA-mismatched cGVHD (B10.D2 → BALB/c) | Induce anergy of Ag-specific T cells | Cutaneous GVHD ↓ | 129 |
| Host-type DCs days 2, 9, and 16 or days 18, 25, and 32 vs short-course rapamycin | TNF-α, IL-12p70, and IFN-γ ↓ | |||
| Induce Treg | ||||
| Subset (no DC conditioning) | ||||
| CD8α+ DCs | MHC (BALB/c → B6) and miHA (C3H.SW → B6) mismatched | T-cell proliferation ↓ | Survival ↑ | 124 |
| Host-type DCs days −8, −5 to −3, and −1 | IFN-γ and TNF-α ↓ | Histopathology ↓ | ||
| IL-10 ↑ | ||||
| CCR9+ pDCs | MHC-mismatched (BALB/c → B6) | CD40/CD80/CD86 expression ↓ | Survival ↑ | 128 |
| Host-type DCs day 0 (mobilized with Flt3L) | Intermediate expression of MHC class II | |||
| Induce Treg | ||||
| IL-12–producing effector T cells ↓ | ||||
| CD49+CD200R3+ DCs (naturally occurring DCreg) | MHC-matched, miHA-mismatched cGVHD (B10.D2 → BALB/c) | Anergy of Ag-specific T cells | Cutaneous GVHD ↓ | 130 |
| Host-type DCs days 2, 9, and 16 | TNF-α, IL-12p70, and IFN-γ ↓ | |||
| Induce Treg | ||||
| TolDC . | GVHD model; treatment . | Effect on DCs (in vitro) . | Effect on GVHD . | Reference . |
|---|---|---|---|---|
| DC conditioning | ||||
| Rapamycin | MHC-mismatched (B6 → BALB/c) | MHC class II, CD80/CD86 expression ↓ | Survival ↑ | 117 |
| Host-type DCs day 0 | Intact in vivo trafficking | Histopathology ↓ | ||
| Intact CCR5, CCR7, and CD62L | ||||
| VIP | MHC (B6 → BALB/c, BALB/c → B6) and miHA-mismatched (B6 → F1) Host-type DCs day 2 and/or day 5 | Donor CD4+ T-cell Ag-specific response ↓ Induce Treg | Survival ↑ (miHA > MHA; early > late for MHA) | 118 146 |
| SAHA (HDAC inhibitor) | MHC-mismatched (BALB/c → B6) | CD40/CD80 expression ↓ | Survival ↑ | 104 |
| Host-type DCs days −1, 0, and 2 | TNF-α ↓ | |||
| T-cell proliferation ↓ | ||||
| TGF-β, IL-10 + LPS (DCreg)* | MHC-matched, miHA-mismatched cGVHD (B10.D2 → BALB/c) | Induce anergy of Ag-specific T cells | Cutaneous GVHD ↓ | 129 |
| Host-type DCs days 2, 9, and 16 or days 18, 25, and 32 vs short-course rapamycin | TNF-α, IL-12p70, and IFN-γ ↓ | |||
| Induce Treg | ||||
| Subset (no DC conditioning) | ||||
| CD8α+ DCs | MHC (BALB/c → B6) and miHA (C3H.SW → B6) mismatched | T-cell proliferation ↓ | Survival ↑ | 124 |
| Host-type DCs days −8, −5 to −3, and −1 | IFN-γ and TNF-α ↓ | Histopathology ↓ | ||
| IL-10 ↑ | ||||
| CCR9+ pDCs | MHC-mismatched (BALB/c → B6) | CD40/CD80/CD86 expression ↓ | Survival ↑ | 128 |
| Host-type DCs day 0 (mobilized with Flt3L) | Intermediate expression of MHC class II | |||
| Induce Treg | ||||
| IL-12–producing effector T cells ↓ | ||||
| CD49+CD200R3+ DCs (naturally occurring DCreg) | MHC-matched, miHA-mismatched cGVHD (B10.D2 → BALB/c) | Anergy of Ag-specific T cells | Cutaneous GVHD ↓ | 130 |
| Host-type DCs days 2, 9, and 16 | TNF-α, IL-12p70, and IFN-γ ↓ | |||
| Induce Treg | ||||
VIP indicates vasoactive intestinal peptide; and LPS, lipopolysaccharide.
Depleted of CD40+CD80+CD86+ cells.