Vening with DCs between donor and recipient on graft survival was 79831-76-8 different from that observed by Oluwole et al with the allopeptide-pulsed group. This suggests that the mechanism of each intervention method may be worth investigating. Coculture largely induced a DC phenotype (KSCDC) with reduced MHC-II expression, increased CD80 expression, and the ability to suppress T cell responses [14]. Co-cultured recipient DCs failed to promote graft survival, which may be related to the strength of the direct allorecognition pathway being activated early after transplantation.Gene modification of Tol-DCs prolonged graft survival. Different gene-modified Tol-DCs such as thosesignificantly prolonged the average survival to over 39 days compared to the control group (P,0.01, derived from original study). They demonstrated that infusion of mature dendritic cells (mDC) and imDC without drug treatment MedChemExpress JSI124 showed no obvious effect on islet allograft survival, and mature, but not immature, VAF347-BMDCs could promote long-term islet allograft survival (Figure 4 B). The authors speculated that VAF347-treated imDCstargeted on CTLA-4, IL-10, and GAD65/DCR3, significantly prolonged survival compared to controls (8.9964.75 d, P,0.05, derived from original study) (Figure 6 A). Unexpectedly, O’Rourke et al demonstrated that the addition of three preoperative doses of cells to the two peri-operative ones did not result in a significant increase in allograft survival, compared with the regimen consisting of only two peri-operative doses [15] (Figure 6 B). ThisFigure 2. Effects of imDC on islet allograft survival. Key information is displayed for each group as follows (L to R): Group name and average survival extension (days) in each group, included study name, main intervention method, survival time of experimental and control groups, survival differentials between experimental and control groups, and P-value from original study (where possible). This structure in describing the figure also applies to the following figures. doi:10.1371/journal.pone.0052096.gInfusion Tol-DC Prolongs Islet Allograft SurvivalFigure 3. Effects of allopeptide-pulsed host Tol-DCs on islet graft survival. A) Single-injection of alloAg-imDC. B) AlloAg-imDC plus ALS group. imDC-alloAg: Allopeptide-pulsed imDC. doi:10.1371/journal.pone.0052096.gsuggests that additional injections did not contribute more to promoting survival, but instead increased the risk and cost. Other derived Tol-DC prolonged grafts survival. Three studies used Tol-DCs derived from donor spleen or liver. Compared to controls, Tol-DCs prolonged graft survival (2.666.89 d), while only liver-derived DCs favored islet allograft survival, and donor spleen-derived DCs showed rejection episodes in two studies (Figure 7 A). Kim et al. demonstrated pre-treatment of hosts with either CD4+DCs or CD8+DCs did not produce prolonged islet allograft survival compared with controls, but did prolong survival when combined with antiCD154Ab [16] (Figure 7 B). Furthermore, the provision of anti-CD154Ab plus CD4+DCs created tolerance, but not CD8+DCs (Figure 7 B). This suggeststhat DC subsets and co-stimulatory signals play an important role on graft survival. Beyond that, Chaib et al. reported animals receiving intrathymic inoculation with liver non-parenchymal cells (NPC) or spleen DCs plus ALS, rejected islet allografts. This is in contrast to their 12926553 previously published work where tolerance to cardiac grafts was induced by intrathymic NPC in.Vening with DCs between donor and recipient on graft survival was different from that observed by Oluwole et al with the allopeptide-pulsed group. This suggests that the mechanism of each intervention method may be worth investigating. Coculture largely induced a DC phenotype (KSCDC) with reduced MHC-II expression, increased CD80 expression, and the ability to suppress T cell responses [14]. Co-cultured recipient DCs failed to promote graft survival, which may be related to the strength of the direct allorecognition pathway being activated early after transplantation.Gene modification of Tol-DCs prolonged graft survival. Different gene-modified Tol-DCs such as thosesignificantly prolonged the average survival to over 39 days compared to the control group (P,0.01, derived from original study). They demonstrated that infusion of mature dendritic cells (mDC) and imDC without drug treatment showed no obvious effect on islet allograft survival, and mature, but not immature, VAF347-BMDCs could promote long-term islet allograft survival (Figure 4 B). The authors speculated that VAF347-treated imDCstargeted on CTLA-4, IL-10, and GAD65/DCR3, significantly prolonged survival compared to controls (8.9964.75 d, P,0.05, derived from original study) (Figure 6 A). Unexpectedly, O’Rourke et al demonstrated that the addition of three preoperative doses of cells to the two peri-operative ones did not result in a significant increase in allograft survival, compared with the regimen consisting of only two peri-operative doses [15] (Figure 6 B). ThisFigure 2. Effects of imDC on islet allograft survival. Key information is displayed for each group as follows (L to R): Group name and average survival extension (days) in each group, included study name, main intervention method, survival time of experimental and control groups, survival differentials between experimental and control groups, and P-value from original study (where possible). This structure in describing the figure also applies to the following figures. doi:10.1371/journal.pone.0052096.gInfusion Tol-DC Prolongs Islet Allograft SurvivalFigure 3. Effects of allopeptide-pulsed host Tol-DCs on islet graft survival. A) Single-injection of alloAg-imDC. B) AlloAg-imDC plus ALS group. imDC-alloAg: Allopeptide-pulsed imDC. doi:10.1371/journal.pone.0052096.gsuggests that additional injections did not contribute more to promoting survival, but instead increased the risk and cost. Other derived Tol-DC prolonged grafts survival. Three studies used Tol-DCs derived from donor spleen or liver. Compared to controls, Tol-DCs prolonged graft survival (2.666.89 d), while only liver-derived DCs favored islet allograft survival, and donor spleen-derived DCs showed rejection episodes in two studies (Figure 7 A). Kim et al. demonstrated pre-treatment of hosts with either CD4+DCs or CD8+DCs did not produce prolonged islet allograft survival compared with controls, but did prolong survival when combined with antiCD154Ab [16] (Figure 7 B). Furthermore, the provision of anti-CD154Ab plus CD4+DCs created tolerance, but not CD8+DCs (Figure 7 B). This suggeststhat DC subsets and co-stimulatory signals play an important role on graft survival. Beyond that, Chaib et al. reported animals receiving intrathymic inoculation with liver non-parenchymal cells (NPC) or spleen DCs plus ALS, rejected islet allografts. This is in contrast to their 12926553 previously published work where tolerance to cardiac grafts was induced by intrathymic NPC in.
