Ination: n =R-DC:n = 1 D-DC:n =D1 Hauben(2008)(D)H-(R)H-mDC-VAF347 (17) imDC+VAF347 (19) mDC (14) imDC (18)!!q -YTHY/R-DCTotleMHC total mismatch: n = 1 (D)H-2dMonotherapy: n = 1 Combination: n =R-DC:n = 1 D-DC:n =EHuang(2010)7 (R)H-2bR-KSC+D-DC R-KSC+R-DC!!q -Y–/R/D-DCTotleMHC total mismatch: n = 1 (R)H-2b (D)H-2d (T)H-2kMonotherapy: n = 1 Combination: n = 0 CD4+imDC+anti-CD154Ab (6) CD4+imDC+antiCD154Ab+ anti-IL10R Ab(4) CD4+imDC (6) CD8+imDC (6) CD8+imDC+anti-CD154Ab (6)R-DC:n = 1 D-DC:n =FKim(2006)!!.120d Y .120d -THY/D-spleen DCFRastellini(1995)9 (R)H-2b(D)H-2kliver-imDC(10) spleen-imDC (4)!!q -Y///D-liver DCInfusion KN-93 (phosphate) custom synthesis Tol-DC Prolongs Islet Allograft SurvivalTable 2. Cont.NO. StudyAnimal model(Mice/Rat)Tol-DC(Number) (total number)Controls C1 COutcomes O1 O2 O3 O4 ODC(R/D)Untreated Negative SUR F3 Chaib(1994)10 (D)RT-uMLR CK / /Treg CTL / / DspleenDC(R)RT-lDC+ALS (9) NPC+ALS (8)!-TotleMHC total mismatch: n =Monotherapy: n = 3 Combination: n =R-DC:n = 0 D-DC:n =A1: Immature dendritic cells (imDC) group. B1?: Allopeptide-pulsed group. C1?: Gene modification group. D1: Drug intervention group. E1: ITI214 Mesenchymal stem cell (MSC) induction group. F1?: Other derived group. “ ” Articles did not report the sample size. “/” Articles did not report relevant information. “-” No difference between experiment group and control group. H-2b: C57. H-2d: BAL/C. H-2k: C3H. RT-1u: WF/WAG. RT-1a: ACI. RT-1n: BN. RT-1l: Lewis. D: Donor. R: Recipient. T: The third party. MHC: Major histocompatibility complex. BMDC: Bone marrow dendritic cell. Ag: Antigen. R-KSC: Host kidney-derived MSC. NPCs: Non-parenchymal cells. ALS: Anti-lymphocyte serum. P5: MHC Class I peptide five. D-DC: Donor-derived DC. R-DC: Recipient-derived DC. SUR: Survival, “q” Prolongation. MLR: Mixed lymphocyte reaction, “Y” Successfully induced donor specific T cell hyporesponsiveness. CK: Cytokine. CTL: Cytotoxic T lymphocyte, “Y” Reduced cytotoxicity against allografts. Treg: Regulatory T cells, “Y” Successfully induced Treg. doi:10.1371/journal.pone.0052096.timmune tolerance (.100 d) (Figure 2). We speculate that Tol-DCs increased generation of donor-specific CD42CD252 Treg cells in recipients transplanted with allogeneic islets depleted of donor “passenger” DCs, after cultured in bioreactors [10].Allopeptide-pulsed host Tol-DCs prolonged graft survival. Three studies adopted a rat islet transplantationwere ineffective because they encountered in vivo pro-inflammatory signals, which reversed their tolerogenic phenotype [13].Mesenchymal Stem Cell (MSC) induction of Tol-DCs prolonged graft survival. Donor but not recipient DCs,model with an intrathymic route of administration. Infusion allopeptide-pulsed host Tol-DCs prolonged graft survival compared to controls (42.14644 d) (Figure 3 A). However, we could not rule out positive effects of intrathymic injection on graft survival. Interestingly, Oluwole et al reported donor-derived DCs did not favor survival, which was opposite to results observed with recipient-derived DCs [11]. One study reported the synergistic effect of anti-lymphocyte (ALS) serum with Tol-DCs, which showed marked prolongation of permanent islet allograft survival (.100 days) (Figure 3 B) [12].Drug intervention of Tol-DCs prolonged graft survival. As shown in Figure 4, drug treatment of Tol-DCscultured with host kidney-derived MSCs (KSCs), prolonged islet allograft 12926553 survival (23 days, P,0.01, derived from original study) (Figure 5 A, B). The effect of inter.Ination: n =R-DC:n = 1 D-DC:n =D1 Hauben(2008)(D)H-(R)H-mDC-VAF347 (17) imDC+VAF347 (19) mDC (14) imDC (18)!!q -YTHY/R-DCTotleMHC total mismatch: n = 1 (D)H-2dMonotherapy: n = 1 Combination: n =R-DC:n = 1 D-DC:n =EHuang(2010)7 (R)H-2bR-KSC+D-DC R-KSC+R-DC!!q -Y–/R/D-DCTotleMHC total mismatch: n = 1 (R)H-2b (D)H-2d (T)H-2kMonotherapy: n = 1 Combination: n = 0 CD4+imDC+anti-CD154Ab (6) CD4+imDC+antiCD154Ab+ anti-IL10R Ab(4) CD4+imDC (6) CD8+imDC (6) CD8+imDC+anti-CD154Ab (6)R-DC:n = 1 D-DC:n =FKim(2006)!!.120d Y .120d -THY/D-spleen DCFRastellini(1995)9 (R)H-2b(D)H-2kliver-imDC(10) spleen-imDC (4)!!q -Y///D-liver DCInfusion Tol-DC Prolongs Islet Allograft SurvivalTable 2. Cont.NO. StudyAnimal model(Mice/Rat)Tol-DC(Number) (total number)Controls C1 COutcomes O1 O2 O3 O4 ODC(R/D)Untreated Negative SUR F3 Chaib(1994)10 (D)RT-uMLR CK / /Treg CTL / / DspleenDC(R)RT-lDC+ALS (9) NPC+ALS (8)!-TotleMHC total mismatch: n =Monotherapy: n = 3 Combination: n =R-DC:n = 0 D-DC:n =A1: Immature dendritic cells (imDC) group. B1?: Allopeptide-pulsed group. C1?: Gene modification group. D1: Drug intervention group. E1: Mesenchymal stem cell (MSC) induction group. F1?: Other derived group. “ ” Articles did not report the sample size. “/” Articles did not report relevant information. “-” No difference between experiment group and control group. H-2b: C57. H-2d: BAL/C. H-2k: C3H. RT-1u: WF/WAG. RT-1a: ACI. RT-1n: BN. RT-1l: Lewis. D: Donor. R: Recipient. T: The third party. MHC: Major histocompatibility complex. BMDC: Bone marrow dendritic cell. Ag: Antigen. R-KSC: Host kidney-derived MSC. NPCs: Non-parenchymal cells. ALS: Anti-lymphocyte serum. P5: MHC Class I peptide five. D-DC: Donor-derived DC. R-DC: Recipient-derived DC. SUR: Survival, “q” Prolongation. MLR: Mixed lymphocyte reaction, “Y” Successfully induced donor specific T cell hyporesponsiveness. CK: Cytokine. CTL: Cytotoxic T lymphocyte, “Y” Reduced cytotoxicity against allografts. Treg: Regulatory T cells, “Y” Successfully induced Treg. doi:10.1371/journal.pone.0052096.timmune tolerance (.100 d) (Figure 2). We speculate that Tol-DCs increased generation of donor-specific CD42CD252 Treg cells in recipients transplanted with allogeneic islets depleted of donor “passenger” DCs, after cultured in bioreactors [10].Allopeptide-pulsed host Tol-DCs prolonged graft survival. Three studies adopted a rat islet transplantationwere ineffective because they encountered in vivo pro-inflammatory signals, which reversed their tolerogenic phenotype [13].Mesenchymal Stem Cell (MSC) induction of Tol-DCs prolonged graft survival. Donor but not recipient DCs,model with an intrathymic route of administration. Infusion allopeptide-pulsed host Tol-DCs prolonged graft survival compared to controls (42.14644 d) (Figure 3 A). However, we could not rule out positive effects of intrathymic injection on graft survival. Interestingly, Oluwole et al reported donor-derived DCs did not favor survival, which was opposite to results observed with recipient-derived DCs [11]. One study reported the synergistic effect of anti-lymphocyte (ALS) serum with Tol-DCs, which showed marked prolongation of permanent islet allograft survival (.100 days) (Figure 3 B) [12].Drug intervention of Tol-DCs prolonged graft survival. As shown in Figure 4, drug treatment of Tol-DCscultured with host kidney-derived MSCs (KSCs), prolonged islet allograft 12926553 survival (23 days, P,0.01, derived from original study) (Figure 5 A, B). The effect of inter.
