Blood Platelets ; physiology ; Cytokines ; blood ; Drug Therapy, Combination ; Humans ; Immune Tolerance ; Thrombocytopenia ; drug therapy ; etiology ; immunology

Chlamydia ; immunology ; pathogenicity ; physiology ; Histocompatibility Antigens Class I ; biosynthesis ; immunology ; Humans ; Immune Tolerance ; immunology ; Muramidase ; immunology

OBJECTIVETo review the recent studies about the role of indoleamine 2,3-dioxygenase (IDO) in tumor induced tolerance.

DATA SOURCESPublished articles (1978 - 2009) on IDO and tumor induced tolerance were selected from Medline.

STUDY SELECTIONArticles selected were relevant to development of IDO in tumor induced tolerance. Of all originally identified articles, 50 specially addressed the stated purpose.

RESULTSRecent work has revealed IDO at high levels in tumors and in tumor-draining lymph nodes and a close relationship between IDO activity and the regulatory T cells.

CONCLUSIONUp-regulation of IDO is proven to be a mechanism of acquired tolerance in tumors, in which the closely coupled positive feedback system between IDO and regulatory T cells may be considered to play an important role.

Animals ; Gene Expression Regulation, Neoplastic ; physiology ; Humans ; Immune Tolerance ; physiology ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Neoplasms ; enzymology ; immunology

BACKGROUNDMany researches demonstrate that the secondary brain injury which is caused by autoimmune attack toward brain antigens plays an important role in surgical brain injury (SBI). Although traditional immunosuppression can reduce autoimmune attack, it will lower the body immunity. Immune tolerance, by contrast, not only does not lower the body immunity, but also could lighten autoimmunity. This study used thymus tolerance to develop an immune system that is tolerant to autologous cerebrospinal fluid (CSF) and autologous brain tissue so that autoimmune injury can be suppressed following the disruption of the blood-brain barrier, thereby reducing brain damage.

METHODSEighty experimental rabbits were divided into five groups by random number table method: 16 in SBI group (group A), 16 in SBI+CSF drainage group (group B), 16 in SBI+CSF drainage+PBS injection group (group C), 16 in SBI+CSF drainage+CSF intrathymic injection group (group D), and 16 in SBI+brain homogenate intrathymic injection group (group E). Rabbits' CSF was drained in group B; was drained and injected PBS into thymus in group C; was drained and injected CSF into thymus in group D; and was injected brain homogenate in group E. Half of the rabbits in each group were phlebotomized on 1st, 3rd, 7th, and 14th days to observe the changes in IL-l, TGF-β by ELISA test, and CD4CD25 regulatory T cells ratio by flow cytometry, and in other animals brain tissues were taken on 7th day for exploring FasL expression by RT-PCR. The least significant difference (LSD) test was used to make paired comparisons; P < 0.05 was considered statistically significant.

RESULTSThe levels of FasL, TGF-β, and the ratios of CD4CD25 regulatory T cells in groups D and E were apparently higher than those in other three groups (P < 0.05). Likewise, the levels of IL-1 in these two groups were lower than the other three groups (P < 0.05). Moreover, the ratios of CD4CD25 regulatory T cells and the levels of TGF-β in groups B and C were higher than those in group A, but the level of IL-1 was lower than that in group A (P < 0.05). There was no significant difference between groups B and C, and groups D and E.

CONCLUSIONThymic injection of CSF and brain homogenate may be able to reduce inflammation after SBI, so thymus immune tolerance may be a useful therapy to treat SBI.

Animals ; Autoantigens ; administration & dosage ; Brain ; surgery ; Brain Injuries ; etiology ; therapy ; Immune Tolerance ; physiology ; Rabbits ; Thymus Gland ; immunology

The study was aimed to compare the effects of T-cell suppression mediated by mesenchymal stem cells (MSC) from normal individuals and myelodysplastic syndromes (MDS) patients. MSC were cultured from the bone marrow of 12 healthy volunteers and 12 MDS patients, the morphology, surface markers and expression of several cytokines of MSC from normal individuals and MDS patients were compared, and the effects of T-cell suppression were tested in the following assays: phytohemaglutinin (PHA)-primed cultures, mixed lymphocyte reaction (MLR), cell cycle of T-cell after PHA-primed cultures and apoptosis of T-cell as well. The results showed that the MSC from normal individuals and MDS patients were similar in morphology, proliferation and surface markers. The suppressions of T-cell proliferation induced by PHA and alloantigens mediated by MDS-MSC were significantly lower than that of normal MSC. More T-cells were arrested in G0/G1 phase by normal MSC, while the effects were deficient by MDS-MSC. The suppression of T-cell activation mediated by MDS-MSC was also lower than that of normal MSC, but suppression effect on T-cell apoptosis increased. The cytokines TGF-beta1, 3, FasL expressed by MDS-MSC were reduced as compared with normal MSC, but TGF-beta2 expression increased in MDS-MSC. It is concluded that although the morphology, proliferation and cell surface markers of MDS-MSC are normal, the T-cell suppression mediated by MDS-MSC is deficient as compared with normal controls. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined.
Adult ; Aged ; Bone Marrow Cells ; cytology ; physiology ; Female ; Humans ; Immune Tolerance ; immunology ; physiology ; Male ; Mesenchymal Stromal Cells ; immunology ; physiology ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; pathology ; T-Lymphocytes ; immunology

Adaptor Proteins, Signal Transducing ; Animals ; Antigens, Differentiation ; physiology ; Asthma ; etiology ; Humans ; Immune Tolerance ; Immunity, Innate ; Membrane Glycoproteins ; physiology ; Myeloid Differentiation Factor 88 ; Proteins ; physiology ; Receptors, Cell Surface ; physiology ; Receptors, Immunologic ; physiology ; Signal Transduction ; Toll-Like Receptors

The profound graft-versus-leukemia (GVL) effect presented after allogeneic hematopoietic cell transplantation (allo-HSCT) has been evidenced. In contrast to T cell mediated GVL, natural killer (NK) cells recognize target cells and introduce GVL effect by using an integration of activating and inhibitory receptors. This review has summarized current literatures from 2001 - 2003 on human killer cell immunoglobulin receptors (KIR) and other NK cell receptors involved in recognition of tumor targets and the polymorphism of KIR genes of donor/recipient pairs of related and unrelated Allo-HSCT. KIR epitope mismatch may facilitate engraftment and reduce leukemia relapse post transplant by mediating lysis of recipient's cells and introducing GVL effect under the condition of KIR epitope mismatch. Clinical roles of KIR in Allo-HSCT and immunotherapy are discussed. Technologic approach in allogeneic reactive NK cells introduction, identification and selection in vitro, development of inhibitory receptor blockade as well as up-regulation of activating NK cells may significantly enhance GVL immune response. Further investigation on the regulation of KIR inhibitory receptors enables to design novel strategy in cancer immunotherapy over the forthcoming decade.
Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; Killer Cells, Natural ; immunology ; Major Histocompatibility Complex ; Receptors, Immunologic ; chemistry ; genetics ; physiology ; Receptors, KIR ; Transplantation, Homologous

Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.
Apoptosis ; Cell Transplantation ; adverse effects ; Cytokines ; physiology ; Graft vs Host Reaction ; Humans ; Immune Tolerance ; Infant, Newborn ; Infant, Premature ; immunology ; Transplantation, Homologous

Adoptive Transfer ; Animals ; CD40 Antigens ; physiology ; CD40 Ligand ; physiology ; Graft Survival ; Immune Tolerance ; Interleukin-10 ; physiology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Sirolimus ; therapeutic use ; T-Lymphocytes, Regulatory ; physiology

BACKGROUNDExperimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.

METHODSEAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.

RESULTSBMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.

CONCLUSIONSIL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.

Animals ; Autoimmune Diseases ; immunology ; Dendritic Cells ; physiology ; Immune Tolerance ; Interleukin-10 ; genetics ; Lymphocyte Activation ; Male ; Myocarditis ; immunology ; Myosins ; immunology ; NF-kappa B ; physiology ; Rats ; Rats, Inbred Lew ; Signal Transduction ; Transfection