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

OBJECTIVETo explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).

METHODSOne hundred and eighty-five chronic HBV carriers in ITP, seen in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to December 2010, were admitted in an observational study under the guidance of CM. Patients' CM symptoms and signs, demographics, liver biochemistries, and qualitative HBV DNA were recorded in the questionnaires. CM syndromes were then differentiated to 15 detailed types and analyzed by generalization. Lastly, the location, pathogenic factors and nature of the disease were also assessed.

RESULTSWhen CM syndrome patterns were differentiated to 15 types, there were 27 (15%) no syndrome cases, 94 (50%) single syndrome cases and 64 (35%) compound syndromes cases. The main detailed syndromes included Liver (Gan)-qi depression (LQD), Kidney (Shen)-qi deficiency (KQD), Spleen (Pi)-qi deficiency (SQD) and Kidney-yang deficiency (KYAD). After CM syndromes generalized to five types, their frequency was Spleen-Kidney deficiency (SKD)>LQD>inner dampness-heat retention (IDHR)>Liver-Kidney deficiency (LKD)>blood stasis blocking collateral (BSBC). SKD and LQD occupied 64%. The disease location included Liver, Gallbladder (Dan), Spleen, Stomach (Wei) and Kidney. The pathogenic factors were mainly qi stagnation, qi deficiency, yang deficiency, concurrently dampness-heat and blood stasis. The deficiency syndrome was more than excess syndrome in its nature.

CONCLUSIONSMost of chronic HBV carriers in ITP have their CM syndrome, and the most common types are SKAD, LQD. This study suggests that the natural history may be improved through breaking the state of immune tolerance or shorten the time of ITP by strengthening Spleen-Kidney and reliving Liver qi.

Adolescent ; Adult ; Biopsy ; Carrier State ; immunology ; Child ; Child, Preschool ; Female ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Humans ; Immune Tolerance ; Liver ; immunology ; pathology ; virology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Syndrome ; Viscera ; pathology ; Young Adult

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

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

OBJECTIVETo investigate the effects of apoptotic lymphocytes on the secretion of cytokines by hepatic sinusoidal endothelial cells (HSEC).

METHODSHuman HSEC cells were co-cultured for 16 h with allogenetic apoptotic lymphocytes induced by UVB irradiation. The supernatants were collected and the levels of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were detected by Luminex technique.

RESULTSAll the cytokines were down-regulated by about 50% in HSECs after co-culture with the apoptotic lymphocytes as compared with those in the control group (P<0.05).

CONCLUSIONSCo-culture with apoptotic lymphocytes can down-regulate the secretion of pro-inflammatory cytokines in HSECs, which may contribute to tolerogenic microenvironment in the liver.

Apoptosis ; physiology ; Cells, Cultured ; Coculture Techniques ; Cytokines ; secretion ; Down-Regulation ; Endothelial Cells ; cytology ; metabolism ; Humans ; Immune Tolerance ; Interferon-gamma ; secretion ; Interleukin-2 ; secretion ; Liver ; cytology ; Lymphocytes ; cytology ; Tumor Necrosis Factor-alpha ; secretion

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

OBJECTIVETo study the prophylactic effects of nasal tolerance with a dual analogue, Lys262-Ala207, on the mouse model of experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanism.

METHODSMouse model of EAMG was induced by intraperitoneal injection of mAb35. Lys262-Ala207 or PBS was given nasally before 10 days (study group A and control group A) or on the day (study group B and control group B) of immunization for 10 days. Clinical syndromes were evaluated after immunization. Serum level of acetylcholine receptor antibody (AChR-Ab) IgG was detected using ELISA. The number of monouclear cells expressing CD4+ and CD4+ CD25+T from spleen was measured using flow cytometry.

RESULTSCompared with the corresponding control groups, the clinical syndromes were improved (P<0.01) in mice from the study groups A and B. The positive rate of the repetitive nerve stimulation (RNS) test in the study groups A and B was significantly lower than that in the corresponding control groups (P<0.01). The study group A showed lower positive rate of RNS than the study group B (P<0.05). The serum levels of AChR-Ab IgG in the study groups A and B (15.01+/-1.09 and 19.23+/-1.31 microg/mL) decreased compared with that in the corresponding control groups (28.12+/-1.28 and 29.35+/-1.28 microg/mL) (P<0.01). The study group A mice had lower serum AChR-Ab IgG levels than the study group B (P<0.01). The number of CD4+ CD25+T cells in the study groups A (4.516+/-0.598%) and B (3.671+/-0.300%) increased significantly compared with that in the corresponding control groups (2.661+/-0.411% and 2.412+/-0.500%) (P<0.01) and more CD4+ CD25+T cells were found in the study group A than in the study group B (P<0.01).

CONCLUSIONSNasal administration with dual analogues may ameliorate clinical syndromes in EAMG rats, which may be associated with decreased serum AChR-Ab IgG levels and increased number of CD4+ CD25+T cells from spleen.

Administration, Intranasal ; Animals ; Female ; Immune Tolerance ; drug effects ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred C57BL ; Myasthenia Gravis, Autoimmune, Experimental ; immunology ; prevention & control ; Receptors, Cholinergic ; immunology ; T-Lymphocytes, Regulatory ; physiology

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

OBJECTIVE: To investigate the relationship among 3 polymorphisms of GP IIb and the function of GP IIb T13959 G in the platelet transfusion refractoriness(PTR). METHODS: The 26th exon, the 30th exon and the 21st intron of gene GP IIb in 110 individuals were amplified by polymerase chain reaction (PCR), and the PCR products were analyzed with single-strand conformation polymorphism(SSCP) and sequenced to investigate whether there was linkage among the polymorphisms of the gene. Human platelet antigen-3 (HPA-3) gene frequency was detected by Fok I enzyme in 147 patients with hematologic diseases, and was compared with that in 110 normal individuals. Forty-four patients who received apheresis platelet transfusion repeatedly were randomly divided into the HPA-3 homotype group and the control group. The antibodies of the platelet were detected after 3 times of platelet transfusion. RESULTS: There were polymorphisms of gene GP IIb in the 26th, 30th exon and the 21st intron, and the mutations were: T changed into G in 13,959 th of the 26th exon; C changed into T in 16,997 th of the 30th exon; the 9 bps deletion occurred in 11,996-12,004 th of the 21st intron. The 3 polymorphisms had synchronization in the individuals. The results of Fok I enzyme indicated that the frequency of HPA-3a was 83.6% (92/110)and 81.9%(119/147), and that of HPA-3b was 16.4%(18/110) and 19.1%(28/147) in the normal individuals and the patients respectively. There was no significant difference between the patients and normal individuals (P>0.05). After the platelet transfusion, the antibodies of all the cases of the homotype platelet transfusion were negative, but the antibodies in 2 cases of the control group were positive, and there was antibody to HPA-3a in one of the antibodies positive cases. CONCLUSION (1)There is close linkage among the polymorphisms of gene GP IIb, which is T->G in 13 959 th of the 26th exon, C->T in 16,997 th of the 30th exon, and the 9 bps deletion in 11,996-12,004 th in the 21st intron. (2)The gene frequency of HPA-3a/3b is similar in the normal individuals and patients with hematologic diseases. (3) HPA-3 system may be one of the reasons for PTR in Chinese.
Adolescent ; Adult ; Aged ; Antigens, Human Platelet ; immunology ; physiology ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Child ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Immune Tolerance ; Introns ; Male ; Middle Aged ; Platelet Membrane Glycoprotein IIb ; genetics ; immunology ; Platelet Transfusion ; Polymorphism, Single-Stranded Conformational ; Young Adult

Idiopathic thrombocytopenia purpura (ITP) is an autoimmune disease which is characterized by destruction of platelets by macrophages in the reticuloendothelial system. Recent studies suggest that ITP is related to the abnormal activation and apoptosis of T/B cells which lead to failure of immune tolerance. Now it is becoming clear that costimulatory signals are required for full T/B cell activation and assumed to modulate T/B cells responses as well as other aspects of the immune system. This review focuses on the role and state-of-the-art advancements of costimulatory signals in ITP.
Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; Antigens, Differentiation, T-Lymphocyte ; immunology ; B-Lymphocytes ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immune Tolerance ; Inducible T-Cell Co-Stimulator Protein ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Receptors, Tumor Necrosis Factor ; immunology ; Signal Transduction ; physiology ; T-Lymphocytes ; immunology ; physiology