Potential strategies to alter APC numbers or function
| Reagent . | Comment . |
|---|---|
| CAMPATH-1H | Depletes blood DCs118,119 |
| Tissue penetration may be limited and LC (which have low CD52 expression) are not depleted significantly118,120 | |
| CMRF-44 | IgM antibody, which binds to a determinant on activated DCs and is expressed on both peripheral blood DC and migrating LC |
| Induces depletion by complement-mediated cytotoxicity in vitro121 | |
| UV | Ultraviolet (A-B) light leads to host-derived LC migration from the skin and replacement by donor-derived LC progenitors122 |
| Short wavelength ultraviolet irradiation effectively depletes host LC and prevents the induction of GVHD,41 although ultraviolet induces other immunomodulatory effects; translation to human setting has proven problematic123 | |
| Alloreactive NK | Preconditioning of recipient mice with alloreactive donor NK cells lacking inhibitory receptors for host class I MHC induces resistance to the development of GVHD; alloreactive NK cells deplete host CD11c+ DCs20 |
| Clinical applications could include choosing unrelated donors who are mismatched for inhibitory ligands or NK cells from third party donors to deplete host DCs before transplantation | |
| Costimulatory blockade | Inhibit host APC-T cell interactions (see Blazar and Taylor124 for extensive review) |
| Regulatory DC | Adoptive transfer of IL-10/TGFβ conditioned host DCs highly effective at preventing GVHD125 |
| FT720 | Sphingosine-1-phosphate (S-1-P) analog that inhibits GVHD but preserves GVL110 ; DCs express receptors for S-1-P and are therefore potential targets for this drug; administration of FTY720 inhibits DC migration and is associated with a sharp reduction in their capacity to access secondary lymphoid organs111 |
| Reagent . | Comment . |
|---|---|
| CAMPATH-1H | Depletes blood DCs118,119 |
| Tissue penetration may be limited and LC (which have low CD52 expression) are not depleted significantly118,120 | |
| CMRF-44 | IgM antibody, which binds to a determinant on activated DCs and is expressed on both peripheral blood DC and migrating LC |
| Induces depletion by complement-mediated cytotoxicity in vitro121 | |
| UV | Ultraviolet (A-B) light leads to host-derived LC migration from the skin and replacement by donor-derived LC progenitors122 |
| Short wavelength ultraviolet irradiation effectively depletes host LC and prevents the induction of GVHD,41 although ultraviolet induces other immunomodulatory effects; translation to human setting has proven problematic123 | |
| Alloreactive NK | Preconditioning of recipient mice with alloreactive donor NK cells lacking inhibitory receptors for host class I MHC induces resistance to the development of GVHD; alloreactive NK cells deplete host CD11c+ DCs20 |
| Clinical applications could include choosing unrelated donors who are mismatched for inhibitory ligands or NK cells from third party donors to deplete host DCs before transplantation | |
| Costimulatory blockade | Inhibit host APC-T cell interactions (see Blazar and Taylor124 for extensive review) |
| Regulatory DC | Adoptive transfer of IL-10/TGFβ conditioned host DCs highly effective at preventing GVHD125 |
| FT720 | Sphingosine-1-phosphate (S-1-P) analog that inhibits GVHD but preserves GVL110 ; DCs express receptors for S-1-P and are therefore potential targets for this drug; administration of FTY720 inhibits DC migration and is associated with a sharp reduction in their capacity to access secondary lymphoid organs111 |