Dendritic cells (DC) play an important roles in the maintenance of central immune tolerance and peripheral immune tolerance. DC can be involved in formation of autoimmune tolerance by many mechanisms and demonstrate strong plasticity, so that DC become hot issue in the research of transplantation tolerance recently. In this article the DC typing and its role, the indirect pathway of DC-inducing immune tolerance, the F1t3L and apoptotic cell role, the modified DC by genetic engineering and the immune inhibitors were summarized.
Dendritic Cells ; immunology ; Humans ; Immune Tolerance ; Transplantation Tolerance ; immunology

Dendritic cells (DCs), the most prevalent antigen-presenting cell in vivo, had been widely characterized in the last three decades. DCs are present in almost all tissues of the body and play cardinal roles in recognition of microbial agents, autoantigens, allergens and alloantigen. DCs process the microbial agents or their antigens and migrate to lymphoid tissues to present the antigenic peptide to lymphocytes. This leads to activation of antigen-specific lymphocytes. Initially, it was assumed that DCs are principally involved in the induction and maintenance of adaptive immune responses, but now it is evident that DCs also have important roles in innate immunity. These features make DCs very good candidates for therapy against various pathological conditions including malignancies. Initially, DC-based therapy was used in animal models of cancers. Data from these studies inspired considerable optimism and DC-based therapies was started in human cancers 8 years ago. In general, DC-based therapy has been found to be safe in patients with cancers, although few controlled trials have been conducted in this regard. Because, the fundamentals principles of human cancers and animal models of cancers are different, the therapeutic efficacy of the ongoing regime of DC-based therapy in cancer patients is not satisfactory. In this review, we covered the various aspects that should be considered for developing better regime of DC-based therapy for human cancers.
Animals ; Dendritic Cells ; immunology ; transplantation ; Disease Models, Animal ; Humans ; Neoplasms ; immunology ; therapy ; Vaccination ; methods

BACKGROUNDAdvances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.

METHODSImmunofluorescent flow cytometry was used to classify white blood cells (WBCs), the levels of mononuclear cells and DCs (including the dominant subpopulations, plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery.

RESULTSThe total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P < 0.05). Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P < 0.005). There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.

CONCLUSIONThe changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.

Adolescent ; Adult ; Dendritic Cells ; immunology ; Graft Rejection ; immunology ; Humans ; Kidney Transplantation ; adverse effects ; Middle Aged ; Myeloid Cells ; immunology ; Young Adult

Animals ; Burns ; surgery ; Dendritic Cells ; immunology ; Humans ; Mice ; Skin Transplantation ; methods

OBJECTIVETo investigate the anti-tumor effect of dendritic cells (DC) pulsed with G422 glioblastomas RNA in mice bearing intracranially G422 glioblastomas.

METHODSDCs were pulsed in vitro with glioblastomas G422 cell RNA. The tumor-bearing mice were injected intratumorally or subcutaneously with pulsed DCs, PBS, non-pulsed DCs. The survival duration of mice was recorded. Serum levels of cytokine IFN-gamma, IL-2, IL-10, IL-4 were detected. Pathological examination was performed.

RESULTSThe survival duration of mice with DC-based vaccine increased significantly(P<0.01). The serum IFN-gamma level was increased (P<0.01) and IL-10 level was decreased (P<0.05) after treatment. Pathological examination showed necrotic tumor in the treatment mice.

CONCLUSIONDC vaccination can significantly increase survival duration of mice with intratumoral or subcutaneous administration of vaccines.

Animals ; Brain Neoplasms ; immunology ; therapy ; Cancer Vaccines ; immunology ; Dendritic Cells ; immunology ; transplantation ; Glioblastoma ; immunology ; therapy ; Immunotherapy ; methods ; Mice ; RNA, Neoplasm ; immunology ; Random Allocation ; T-Lymphocytes, Cytotoxic ; immunology

BACKGROUND: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigen- presenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. METHODS: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. RESULTS: MSC inhibit the CD83 and HLA- class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-gamma production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. CONCLUSION: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.
Bone Marrow ; Cell Culture Techniques* ; Dendritic Cells* ; Leukemia, Myeloid ; Lymphocytes ; Mesenchymal Stromal Cells* ; T-Lymphocytes ; Transplantation Immunology

The study was aimed to explore the roles of exosomes derived from regulatory dendritic cells of mice in the induction of immune tolerance. Immature DC (iDC) from mouse bone marrow cells and regulatory DCs (rDC) were induced by treating iDC with TGF-beta1 and IL-10. The phenotype of regulatory DCs and normal DCs were assayed by flow cytometry. Exosomes from immature DCs (iDex) and regulatory DCs (rDex) were isolated by ultracentrifugation and ultrafiltration. A skin transplantation model was established with the recipients BALB/c mice and the donor C57BL/6 mice. Recipients were divided into PBS control group, iDex group (injection 10 microg iDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation), rDex group (injection 10 microg rDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation). The capacity of the donor mice and the unrelated allogeneic donor mice to stimulate allogeneic T lymphocyte proliferation was examined by mixed lymphocyte culture (MLR). The results showed that TGF-beta1 and IL-10 could down-regulate the expressions of costimulatory molecules, including CD80, CD86 and CD40. The graft mean survival time (MST) in control group, iDex group and rDex group was 7.8, 10.7 and 18.8 days, respectively. There was significant difference in MST between iDex group and control group (p<0.05), and between rDex group and iDex group (p<0.01). The results of MLR assays indicated donor-specific hyporeactivity especially in rDex group, while the tolerant B/C mice were still immunocompetent to unrelated allogeneic DBA mouse. It is concluded that injection iDex or rDex of donor mice via tail vein before skin transplantation induces immunotolerance, and the effect of rDex is more significant.
Animals ; Dendritic Cells ; cytology ; immunology ; transplantation ; Exosomes ; immunology ; transplantation ; Female ; Graft Enhancement, Immunologic ; methods ; Graft Survival ; Immune Tolerance ; immunology ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Skin Transplantation ; Transplantation Immunology ; Transplantation, Homologous

OBJECTIVETo investigate the effect of CD8(+)CD28(-) suppressor T cells(Ts) induced by dendritic cell(DC) with major histocompatibility complex 1(MHC-1) expression RNA interference on immune tolerance in rat intestinal transplantation.

METHODSThe expression level of CD8(+)CD28(-)Ts were successfully induced by DC with MHC-1 expression interfered by RNA interference technique under the stimulator of allograft antigen. Orthotopic intestinal transplantation was performed in 36 rats by modified three cuffs method. The recipients were randomly divided into three groups(12 rats in each group):group A was experimental group with CD8(+)CD28(-) Ts being administrated, mixed T cells were injected in group B, while in group C, NS were administrated. On the first day and the seventh day posttransplant, the 36 rats of the 3 groups were administrated through vena dorsalis penis respectively. Six rats were selected randomly from each group and the animals were sacrificed on the 14 th day postoperatively, serum levels of TGF-beta, IFN-gamma and the values of Na(+)-K(+)-ATPase activity of the intestinal graft were assayed and the intestinal pathologic morphology, intestinal allograft survival were observed concerning the remainders.

RESULTSOn the 14 th day after operation, the expression levels of TGF-beta and IFN-gamma in group A were significantly up-regulated as compared with those in group B and group C(P<0.05). Na(+)-K(+)-ATPase activity in group A was(6.3+/-1.0) kU/g, much higher than the levels of group B(3.6+/-0.9)kU/g and group C(2.9+/-1.3) kU/g and the differences were significant(P<0.05). The data suggested preliminarily that pathological scores of intestinal graft in group A were lower than those in group B and group C. The survival time of the recipients in group A was 32.0 days, much longer than that in group B (17.5 days, P<0.05) and group C(21.0 days, P<0.05).

CONCLUSIONCD8(+)CD28(-) Ts induced by DC with MHC-1 expression RNA interference can alleviate acute rejection and lead to immune tolerance in rat intestinal transplantation.

Animals ; Dendritic Cells ; immunology ; metabolism ; Immune Tolerance ; Intestine, Small ; immunology ; transplantation ; Major Histocompatibility Complex ; immunology ; Male ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; T-Lymphocytes, Regulatory ; immunology ; Transplantation Tolerance ; immunology ; Transplantation, Homologous ; immunology

Dendritic cells (DCs) are potent antigen-presenting cells for the induction and activation of cytotoxic T lymphocytes. We tested whether bone marrow derived DCs are capable of inducing protective immunity against a murine lymphoma (A20). DCs were grown from tumor-bearing BALB/c mice by culturing bone marrow cells. BALB/c mice were injected (sc) with A20 cells on day 0. Intraperitoneal immunization with DCs mixed with lethally irradiated A20 cells were started when the tumor reached ca. 4-5 mm in diameter (Group A) or on day -7 (Group B). Booster immunizations were given every 3-4 days for four weeks. By 31 days in group A, there was a significant reduction in tumor growth in the mice immunized with DCs mixed with irradiated A20 cells as compared with the control groups (p=0.016). In group B, tumor growth was completely inhibited and there was no tumor growth following extended observations after completion of immunization. Thus, DCs mixed with irradiated tumor cells can induce an antitumor effect. This provides a rationale for the use of DCs mixed with irradiated tumor cells in immunotherapy for minimal residual disease of lymphomas.
Animals ; Apoptosis/immunology ; Bone Marrow Cells/immunology ; Cell Division/immunology ; Cell Line, Tumor ; Dendritic Cells/*immunology/transplantation ; Female ; Immunization/*methods ; Lymphocyte Culture Test, Mixed ; Lymphoma/*immunology/pathology/*therapy ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; T-Lymphocytes, Cytotoxic/immunology

OBJECTIVETo observe the dynamic changes of dendritic cells (DCs) in the renal graft of rats within 72 h after renal transplantation.

METHODSUsing SD rats as the donors and Wistar rats as the recipients, renal transplantation was performed in 30 pairs of rats, with another 5 donor kidneys that were not transplanted serving as the sham operation group. The transplanted kidneys were harvested at 1, 6, 12, 24, 48 and 72 h after recovery of blood circulation, paraffin-embedded and sectioned ,followed by HE staining and immunohistochemical staining for S-100 protein for DC identification. The pathological changes and the DC density per glomerulus in the renal graft were observed with optical microscope.

RESULTSNo signs of acute rejection were found in these sections. Few DCs were observed in the sham operation group and in the renal graft 1 h after transplantation. The number of DCs in the renal graft increased with time and reached the maximum 24 h after transplantation followed by gradual decrease.

CONCLUSIONSWithin 72 h after renal transplantation, the number of DCs in the graft varies following a curve with a single peak. Increased DC density in the graft may result from recipient DC migration into the graft, and accordingly, decreased recipient DC migration results in decrease of DC density in the graft. The pattern of DC number variation in the graft can be helpful to further improve the therapy against graft rejection.

Animals ; Cell Count ; Cell Movement ; immunology ; Dendritic Cells ; cytology ; immunology ; Female ; Graft Rejection ; prevention & control ; Kidney Glomerulus ; immunology ; Kidney Transplantation ; immunology ; Male ; Rats ; Rats, Wistar ; Time Factors