Table 3.
Influence of immunosuppressive drugs, biologic agents and novel immunoregulatory agents on myeloid DC, macrophages and MDSC in vivo.
| Therapeutic Agent | Type of cell | Species/Model | Effect/s on cells | Reference |
|---|---|---|---|---|
| GCs, Dexamethasone | mDCs & Mϕ | Delayed-type hypersensitivity mice | Depletion of mDC and pDC, and Mϕ enrichment | (89) |
| MDSC | Trauma model mice | Expansion of MDSC | (90) | |
| 1α,25(OH)2D3 (VitD3) | DCs | - | Modulation of phenotype and function towards tolerogenic DC | (164, 165) |
| MDSC | Tumor-bearing mice | Diminished presence of MDSC within regional lymph nodes, spleens and tumors, restoration of their Ag-presenting ability and differentiation towards a DC phenotype | (166–168) | |
| Cyclosporine A | DC | D-type hypersensitivity mice | Defective Ag acquisition and MHC-restricted Ag presentation | (169) |
| DC & Mϕ | Rat | Reduced numbers in thymus | (96–98) | |
| Mϕ | Cardiac Tx in NHP (combined with CCR5 blockade) | Generation of alternatively-activated Mϕ | (100) | |
| DC | Heart Tx patients | Increase in circulating mDC percentage | (102) | |
| DC & Mϕ | Mouse kidney Tx model and humans | Reduction in bacterial phagocytosis | (170) | |
| Tacrolimus | DC & Mϕ | LPS-induced inflammatory response (mouse) | Decreased responsiveness to LPS, and blocking of MHC-restricted Ag presentation | (94, 95) |
| Mϕ | Brain-injured rats | Reduction in the number recruited to the inflammatory site, and their proliferative activity | (171) | |
| DC | Atopic dermatitis patients | Decrease in IgE receptors | (172) | |
| Rapamycin | DC | - | Impairment of DC costimulatory molecule up-regulation, production of pro-inflammatory cytokines, and T cell allostimulatory capacity, and induction of apoptosis | (113, 114) |
| Kidney transplant patients | Increased immuno-stimulatory potential | (115) | ||
| Mycophenolate Mofetil(MMF) | DC | Contact hypersensitivity (mice) | Impaired Ag-presenting capacity | (109) |
| Mϕ | Renal Tx rats | Inhibition of Mϕ infiltration | (173) | |
| HDAC inhibitors | DC | Graft-versus-host-disease mice, and humans | Reduced costimulatory molecule expression, pro-inflammatory cytokine release, and T cell allostimulatory activity | (120, 121) |
| Proteasome inhibitors | DC | Mice | Impairment of DC maturation and cytokine production, as well as DC-mediated T cell stimulation | (130) |
| NFκB inhibition: | ||||
| - Azithromycin | DC | Murine histo-incompatibility model | Inhibition of DC maturation | (174) |
| - Liposomes containing NFκB decoy oligodeoxynucleotides (ODN) | Mϕ | Kidney transplantation (rats) | Reduction of periarterial Mϕ infiltration | (175) |
| PGE2 receptor (EP4) agonist | Mϕ | Cardiac Tx mice | Suppression of Mϕ activation | (138) |
| Polyclonal antithymocyte globulin (ATG) Ab | mDC | Allogeneic stem cell Tx patients | Reduction of circulating mDCs | (176) |
| Anti-CD52 mAb | mDC | Kidney transplant patients | Strong and sustained reduction in the total number of peripheral DC and a significant shift from myeloid to plasmacytoid DC subsets | (143) |
| CTLA4Ig | DC | Cardiac Tx rats | Secretion of inhibitory products that suppress alloAg-induced T cell proliferative responses | (151) |
| Anti-CD154 | DC | Cardiac Tx mice | Potentiation of DC tolerogenicity | (156) |
| Anti-CD28 mAb | MDSC | Kidney Tx rat | MDSC accumulation in the blood and allograft | (82) |
| siRNA gene silencing of MyD88 and TRIF | DC | Cardiac Tx mice | Reduction of DC maturation | (158) |
| Recombinant G-CSF (Neupogen) | MDSC (Gr-1+CD11b+) | Skin Tx mice | Induction of a high frequency of MDSC in the peripheral lymphoid compartments | (159) |
| Human ILT2 | MDSC | Skin Tx mice | Increased MDSC (CD11b+Gr-1+) and enhanced long-term survival of allografts | (75) |
Abbreviations: DC, dendritic cell; GCs, glucocorticoids; HDAC, histone deacetylase; ILT2, immunoglobulin-like transcript 2; mDC, myeloid dendritic cell; Mϕ, macrophage; MyD88, myeloid differentiation primary response gene 88; NHP, non-human primate; TRIF, Toll-IL-1 receptor domain containing adaptor-inducing interferon-β; tx, transplant; vitD3, vitamin D3