Table 2.
Ex vivo approaches to generate tDC, phenotypes of the cells, and major effects.
| GM-CSF? | IL-4? | IL-10? | TGFβ? | Other? | Ag provision? | DC phenotype | Effects | Reference(s) |
|---|---|---|---|---|---|---|---|---|
| YES | NO | YES | YES | NO | NO | ↓Costimulatory molecules; ↓ IL-12, IL-23, IL-6; ↑ IL-10 |
Reduces insulitis. Prevents spontaneous diabetes in murine T1D models. Induces Tregs. Induces hyporesponsiveness of T-cells. Inhibits T-cell proliferation | (55, 56) |
| YES | YES | YES | YES | NO | NO | Intermediate expression of MHCII, CD40, CD80, CD86, CD83; ↓ IL- 12p70, IL-23, TNFα; ↑ IL-10, IL-6, PD-L1 |
Decreases T-cell peri-islet infiltration in rodents. Reduces T-cells Proliferation in rodents. Induces Tregs in rodents. Prolongs the survival of syngeneic Islet transplants in NOD mice |
(57–59) |
| YES | YES | YES | YES | Insulin; GAD65 | YES | ↑ CD1a; ↓Costimulatory molecules (CD40, CD86); ↓ CD83; ↓ MHC-II, IL-12; ↓ IL-23; ↑ PGE |
Suppresses effector/memory T-cells in rodent and human experiments. Induces T-cell anergy in rodent studies. Induces Tregs. Induces IL-10 production by T-cells in rodent and human cells. Suppresses T-cell proliferation. Induces hyporesponsiveness of rodent and human T-cells. | (60, 61) |
| YES | YES | NO | NO | Vitamin D+Dexamethasone+Pro-insulin | YES | ↓ MHC-II, IFNγ, CD86; ↑ IL-10, PD-L1 |
Controls autoimmunity in rodent models. Induces Tregs. Inhibits effector T-cells. Eliminates CD8+ T-cells in rodent models. |
(62, 63) |
| YES | YES | NO | NO | Vitamin D+Dexamethasone+GAD65 | YES | ↓Costimulatory molecules (CD40, CD86), CD83, MHC-II; ↑ CD14, TLR-2, PD-L1, IL-10; ↓ IL-6, TNFα, IL-23, IL-12p70 |
Decreases Th1/Th17 responses in rodent models. Suppresses antigen-specific T-cell activation and proliferation in rodent and human experiments. Prevents onset diabetes in NOD-SCID mice. Decreases IFNγ production by T-cells in rodent and human cultures. |
(54, 64) |
| YES | YES | NO | NO | Rapamycin | NO | ↓Costimulatory molecules (CD40, CD80), IL-6, IL-23; ↑ PD-L1 |
Induces Tregs. Inhibits T-cell proliferation in rodent experiments. Reduces Th17 cells in rodent experiments. |
(57, 65) |
| YES | YES | NO | NO | Antisense DNA to primary transcripts of CD40, CD80, and CD86 | NO | ↓Costimulatory molecules (CD40, CD80, CD86), NO, TNFα, IL- 12p70 |
Prevents diabetes in NOD mice. Reduces insulitis. Promotes Tregs. Increases B-cells and Bregs in human and rodent cell cultures. Suppresses human and rodent T-cell proliferation: | (66–68) |
| YES | YES | NO | NO | Pro-insulin | YES | Delays or halts progressive destruction of β cell and loss function in mouse models. | (15) | |
| YES | YES | NO | NO | Liposomes | YES | ↓Costimulatory molecules (CD40, CD86); ↑ PDL1 expression, VEGF secretion |
Arrests autoimmunity in rodent experimental diabetes | (69, 70) |
| YES | YES | NO | NO | TLR ligand | NO | ↑ PD-L1, IRAK-M; Minimum increases of MHC-II, CD40, CD80, CD83, CD86 |
Suppresses T-cell activation and proliferation in rodent cell culture. Delays insulitis in NOD mice | (71) |
| YES | NO | NO | NO | Apoptotic bodies | NO | ↓Costimulatory molecules (CD40, CD86), IL-6, TNFα |
Reduces disease incidence in NOD mice. Reduces insulitis in NOD mice |
(72) |
| YES | NO | NO | NO | Liposomes | YES | ↑ TIM4, CD36; ↓ MHC-II, Costimulatory molecules (CD40, CD86); ↑ CCR7, CCR2, DC-SING; ↓ IL-6; ↑ Anti-inflammatory cytokines (IL-10, TGFβ1) |
Decreases CD8+ T-cell proliferation in rodent cell model. Reduces disease incidence in NOD mice. Reduces insulitis in NOD mice. | (73) |