Research progress on OX40/OX40L axis mediated T cell immunity in the course of oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a common chronic disease of the oral mucosa with unclear pathogenesis. Local infiltration of T cells plays a key role in the pathological process of OLP. Increased evidence supports the notion that the imbalance of helper T cells (Th) 1/Th2 and Th17/regulatory T cells (Treg) and their related cytokines is closely related to the pathogenesis and progression of OLP. In recent years, studies have shown that OX40 (CD134) and its ligand OX40L (CD252) play an important role in the process of the T-cell immune response. They participate in the balance regulation of Th1/Th2 and Th17/Treg, mediate the imbalance of pro-inflammatory and anti-inflammatory, and affect the occurrence and development of a variety of autoimmune diseases. However, there is no direct evidence that the OX40/OX40L axis mediates the imbalance of T-cell subsets in the pathogenesis of OLP. Therefore, large sample clinical as well as in vitro and in vivo experimental studies on the mechanism by which the OX40/OX40L axis regulates the balance of T-cell subsets in OLP are still needed in the future.

Samsum ant venom modulates the immune response and redox status at the acute toxic dose in vivo

Background:Ant venoms express surface molecules that participate in antigen presentation involving pro- and anti-inflammatory cytokines. This work aims to investigate the expression of MHC-II, CD80 and CD86 on the polymorphonuclear cells (PMNs) in rats injected with samsum ant venom (SAV).Methods:Rats were divided into three groups - control, SAV-treated (intraperitoneal route, 600 μg/kg), and SAV-treated (subcutaneous route, 600 μg/kg). After five doses, animals were euthanized and samples collected for analysis.Results:The subcutaneous SAV-trated rats presented decreased levels of glutathione with increased cholesterol and triglyceride levels. Intraperitoneal SAV-treated animals displayed significantly reduced concentrations of both IFN-γ and IL-17 in comparison with the control group. However, intraperitoneal and subcutaneous SAV-treated rats were able to upregulate the expressions of MHC-II, CD80 and CD86 on PMNs in comparison with the control respectively. The histological examination showed severe lymphocyte depletion in the splenic white pulp of the intraperitoneal SAV-injected rats.Conclusion:Stimulation of PMNs by SAV leads to upregulation of MHC-II, CD 80, and CD 86, which plays critical roles in antigen presentation and consequently proliferation of T-cells. Subcutaneous route was more efficient than intraperitoneal by elevating MHC-II, CD80 and CD86 expression, disturbing oxidative stability and increasing lipogram concentration.

Expressions and clinical significance of inducible co-stimulator and inducible co-stimulator ligand in peripheral blood of patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To investigate the expression of inducible co-stimulator (ICOS) and inducible co-stimulator ligand (ICOSL) on PBMCs,and the plasma concentrations of soluble forms of ICOSL and their clinical relationship with systemic lupus erythematosus (SLE) patients.Methods Peripheral blood samples were collected from 45 SLE patients and 39 healthy subjects (HC).The expressions of ICOS and ICOSL on peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry.The concentrations of soluble ICOSL were assessed by measured by enzyme linked immunosorbent assay (ELISA).And the relationship between their expression levels and patients' clinical manifestations were analyzed.Levene F test was used for statistical analysis,the comparison between groups was conducted using t test,and the correlation between two variables were tested by Pearson correlation analysis.Results The expression of ICOS on CD4+ and CD8+ T cells were significantly higher than that of the HC [(19.1±1.7)％ vs (14.0±1.5)％,t=2.156,P=0.035],[(10.0± 1.0)％ vs (6.4±1.0)％,t=2.587,P=0.012].The expression of ICOSL on CD14+ mononuclear cells in SLE patients was significantly higher than that in the HC group [(2.94±0.88)％ vs (0.89 ±0.21)％,t=2.152,P=0.04].Plasma ICOSL concentrations in patients with active SLE were significantly higher than those of patients with inactive SLE [(362±25) ng/ml vs (278±15) ng/ml,t=2.356,P=0.025].We also found a significant negative correlation between the soluble ICOSL expression and the surface ICOSL expression on both mononuclear cells and B cells (r=-0.4243,P=0.022;r=-0.4099,P=0.025).MMPI induced an evident reduction in sICOSL levels released from the cells,which was statistically significant in comparison with untreated cells (P＜0.05).Conclusion The up-regulated expressions of ICOS and ICOSL on peripheral lymphocytes and the high levels of plasma concentration of soluble ICOSL are closely correlated with the severity of the disease,suggesting that ICOS/ICOSL pathway may play a critical role in the pathogenesis of SLE.

Changes of CD4+, CD8+ T cell proportions and cell surface programmed death-1 level in peripheral blood mononuclear cells of patients with thyroid-associated ophthalmopathy / 第二军医大学学报

Objective To observe the changes of CD4+, CD8+T cell proportions and the level of cell surface programmed death-1 (PD-1) in the peripheral blood mononuclear cells (PBMC) of patients with thyroid-associated ophthalmopathy (TAO), and to explore their roles in the pathogenesis and diagnosis of TAO. Methods The clinical data of 21 TAO patients, 21 Graves disease (GD) patients without ophthalmopathy and 20 healthy volunteers were collected. The proportions of CD4+, CD8+T cells in PBMCs and cell surface PD-1 expressions were tested by flow cytometry and were compared between different groups; and their correlation with disease course, thyroid functions, thyroid associated antibodies and severity of TAO were analyzed. Results (1)The proportions of CD4+, CD8+T cells in PBMCs of TAO patients ([35.9±14.5]% and [22.2±8.4]%, respectively) and GD patients ([33.1±13.0]% and [18.6±9.2]%, respectively) were both significantly higher than those in the healthy volunteers ([17.4±7.4]% and [7.7±4.8]% respectively, both P0.05). Conclusion The aberrant proportions of CD4+, CD8+T cells in PBMCs and cell surface PD-1 expression may participate in the autoimmune process of TAO.

Effect of leflunomide on peripheral blood CD28/CTLA-4 costimulatory molecules expression in guinea pig with EAE / 中国生化药物杂志

Objective To investigate immunological mechanism underlying leflunomide ( LEF ) against experimental allergic encephalomyelitis ( EAE) by studying the effects of LEF on peripheral blood CD28/CTLA-4 costimulatory molecules expression in guinea pig with EAE.Methods 50 adult female guinea pigs were randomly divided into normal control group,low dose group,EAE control group,middle dose group,and high dose group, 10 guinea pigs in each group respectively.Low, medium and high dose group were treated with LEF 10 mg/kg· D, 20 mg/kg· D and 40 mg/kg· D orally, 1 times/day, to the termination of the experiment.The expression of CD28, CTLA-4 were detected by flow cytometry, incidence was recorded at the same time.Results Compared with EAE control group,high dose and middle dose group incubation period were prolonged, progress period were shorten and neurological dysfunction score decreased(P<0.05).Compared with normal control group, the expression of CD28 of EAE control group increased and the decreased expression of CTLA-4 (P<0.05).High, middle dose treatment group compared with EAE control group CD28 down regulated expression (P<0.05), but the expression of CTLA-4 increased(P<0.05).Among the treatment groups, of CD28 molecules with high dose group decreased significantly(P<0.05), the expression of CTLA-4 molecules with high dose treatment groups upregulated significantly (P<0.05).Correlation analysis showed that the EAE control group, the treatment group the CD28/CTLA-4 ratio in peripheral blood and nerve dysfunction score is proportional ( r=0.85, P=0.002; r=0.77, P=0.000).Conclusion LEF can reduce EAE guinea pig neurological symptoms, the better and the higher dose effect.Its mechanism may be through down-regulation of CD28 molecules in peripheral blood, upregulation of the expression of CTLA-4 molecule.so as to reduce the inflammatory response, relieve the clinical symptoms.

Clinical significance of ICOS and ICOSL expression in patients with rheumatoid arthritis / 中国免疫学杂志

Objective:To investigate the expression of inducible costimulatory ( ICOS) and inducible costimulatory ligand ( ICOSL) on peripheral blood mononuclear cells ( PBMCs ) and their clinical relationship with rheumatoid arthritis ( RA ) patients.Methods:Peripheral blood samples were collected from 85 RA patients and 50 HC in this study.Expression of ICOS and ICOSL on PBMC from the subjects were detected by flow cytometry and real-time polymerase chain reaction( RT-PCR).The alteration of ICOS and ICOSL were observed after hormone therapy in 15 patients with RA and the relationship between their expression level and patients′clinical manifestations were analysed.Results:The ICOS and ICOSL mRNA level of RA patients′PBMCs were significantly higher than that in HC.The expression level of ICOS on CD4+T cells was higher than than that in HC[(7.08±4.72)% vs (3.01+1.39)%,P<0.0001].The expression of ICOSL on monocytes[(5.77±3.45)%vs (3.64±1.43)%,P<0.05] and B cells [(5.78± 4.52)%vs (3.97±1.63)%,P<0.05] were significantly elevated in RA patients.In RA patients with active disease,however,ICOSL expression on monocytes and B cells were increased as compared with those in inactive RA patients [ ( 5.45 ±3.50 )% vs ( 4.04 ± 1.55)%,P=0.036],[(6.59 ±5.74)%vs (5.63±4.30)%,P=0.016].Furthermore,after receiving immunosuppressive therapy, the expressions of ICOS and ICOSL were notably reduced as compared with pre-therapy levels on PBMCs from patients [ ( 5.45 ±3.50)%vs (4.04±1.55)%,P=0.036],[(6.59 ±5.74)%vs (5.63±4.30)%,P=0.016].Conclusion:The high levels of ICOS and ICOSL expression were closely correlated with the degree of disease and therapeutic response,suggesting that ICOS/ICOSL pathway may play a critical role in pathogenesis of RA.

Expression of B7-H4 in experimental autoimmune myocarditis / 中国免疫学杂志

Objective:To observe the expression of B7-H4 in experimental autoimmune myocarditis (EAM).Methods:BALB/c mice were randomly divided into 2 groups:the control group and the experimental group.The mice of experimental group were injected with myosin to establish EAM models , while the mice of control group were injected with complete Freund 's adjuvant and normal saline.All the mice were killed separately at the 14th,21st,30th and 45th day for lymphocyte proliferation assay ,hematoxylin-eosin staining,immunohistochemical staining and real-time PCR.Results:The inflammation infiltration of heart was most serious at the 14th and 21st day,then it was gradually relieved with time;the results of lymphocyte proliferation assay and real-time PCR were similar to that of the inflammation infiltration of heart ,which were in high level at the 14th and 21st day,and they were both higher than that of the control group ( P<0.05 );B7-H4 protein were only detected in the experimental group ,and it was constantly expressed during the whole experiment on the endothelium of heart with myocarditis.Conclusion:B7-H4 participates in the progress of EAM ,and it may be a new way of studying the mechanism of myocarditis.

Expression and significance of CD28/B7 family costimulatory molecules mRNA in peripheral blood mononuclear cells of patients with HBV chronic change / 重庆医学

Objective To analyze and evaluate the expression and significance of costimulatory molecules CD 28 ,CTLA-4 ,CD86 , CD80 mRNA in peripheral blood mononuclear cells of the patients with HBV chronic change .Methods The levels of costimulatory molecules CD28 ,CTLA-4 ,CD86 ,CD80 mRNA in peripheral blood mononuclear cells were detected in 24 cases of chronic hepatitis B (CHB) ,24 cases of liver cirrhosis(LC) ,28 cases of hepatocellular cancer(HCC) and 30 normal control(NC) subjects by real time quantitative PCR .Results Compared with the NC group ,costimulatory molecule CD28 mRNA level in the CHB group was signifi-cantly decreased(t= -2 .11 ,P<0 .05);CTLA-4 mRNA level in different diseases groups was decreased to different degrees :the CHB group(t= -2 .52 ,P<0 .05) ,the LC group(t= -2 .11 ,P<0 .05) and the HCC group(t= -2 .56 ,P<0 .05);CD86 mRNA level in different diseases groups was decreased to different degrees too :the CHB group(t= -3 .68 ,P<0 .01) ,the LC group(t= -2 .99 ,P<0 .01) and the HCC group(t= -4 .42 ,P< 0 .01);CD28/CTLA-4 mRNA level was significantly increased in the HCC group(t= 2 .12 ,P< 0 .05);CD80/CD86 mRNA level was significantly increased to different degrees with the progress of HBV chronic change:the CHB group(t=2 .10 ,P<0 .05) ,the LC group(t=2 .59 ,P<0 .05) and the HCC group(t=3 .74 ,P<0 .01) . Conclusion The expression abnormality of CD28/B7 family costimulatory molecules mRNA in HBV infectious patients may be closely related with the immune dysfunction and the development and progression of the chronic change .

Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy

Leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. We studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. The expression of the costimulatory molecules was evaluated in in vitro-stimulated peripheral blood mononuclear cells of lepromatous and tuberculoid patients and healthy exposed individuals (contacts). We show that LL patients have defective monocyte CD86 expression, which likely contributes to the impairment of the antigen presentation process and to patients anergy. Accordingly, CD86 but not CD80 blockade inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the LL anergy, there was reduced expression of the positive signalling costimulatory molecules CD28 and CD86 on the T-cells in these patients. In contrast, tuberculoid leprosy patients displayed increased expression of the negative signalling molecules CD152 and programmed death-1 (PD-1), which represents a probable means of modulating an exacerbated immune response and avoiding immunopathology. Notably, the contacts exhibited proper CD86 and CD28 expression but not exacerbated CD152 or PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signalling.

Effect of leflunomide on the superflcial costimulatory molecules spectrum of peripheral blood T lymphocytes in patients with lupus nephritis / 中华风湿病学杂志

Objective To investigate the effect of leflunomide on the superficial costimulatory molecules expression of T lymphocytes in patients with lupus nephritis ( LN ). Methods The peripheral blood mononuclear cells (PBMCs) of female active LN patients and healthy female were separated by density gradient centrifugation, and cultured by phytohemagglutinin (PHA) or leflunomide active metabolites(A771726).The CD28, CD40L, CTLA-4 and LFA-1a expressions on the peripheral blood T lymphocytes were detected by double-colored flow cytometry. The differences of the means were tested by analysis of variance( ANOVA ) and SNK q test. Results Comparing with healthy controls, there were significantly higher expressions of CD28,CD40L, LFA-1a and CTLA-4 on the peripheral blood T cells in active LN patients (CD28:33.4±6.5 vs14.4±3.2; CD40L: 13.2±3.2 vs 5.4±2.3; LFA-1a: 8.5±2.3 vs2.2±1.1; CTLA-4:4.6±1.5 all P＜0.01) as well as CD28 and CD40L expression on the peripheral blood T cells from healthy controls induced by PHA (CD28:26.8±6.7 vs14.4±3.2; CD40L: 13.9±4.9 vs 5.4±2.3 all P＜0.01 ), but not CTLA-4 and LFA-1a expression.However, CD28, CD40L, LFA-1a and CTLA-4 expressions on T cells stimulated by PHA increased in active LN patients(all P＜0.05 ). A771726 could significantly inhibit over-expression of LFA-1a and CD40L on the T cells from active LN patients (CD40L:8.2±2.0 vs13.3±3.2;LFA-1a:5.1±1.3 vs8.5±2.3 all P＜0.01 ), but not CD28 and CTLA-4 expression. A771726 did not inhibit CD28, CD40L, LFA-1a and CTLA-4 expression on the T cells in healthy controls. Furthermore, A771726 could markedly inhibit the over-expression of all of the above molecules induced by PHA on the T cells of active LN patients (all P＜0.05). Conclusion One of the major mechanisms for LEF treatment of LN is that LEF can down-regulate CD40L and LFA-1a expression but not CD28 and CTLA-4 expression on the peripheral blood T cells in active LN patients.

Expression of activating and inhibitory receptors as well as costimulatory molecules on peripheral blood natural killer cells in patients with recurrent genital herpes / 中华皮肤科杂志

Objective To investigate the expression of activating receptors (NKG2D and NKp46), inhibitory receptors (NKG2A and KIR) as well as costimulatory molecules (OX40, 4-1BB and ICOS) on peripheral blood natural killer (NK) cells from patients with recurrent genital herpes (RGH). Methods Four-color immunofluorescence staining with flow cytometry was used to detect the expression of NKG2D, NKG2A, KIR and NKp46 in 44 patients with RGH and 40 normal human controls, and to detect the expression of OX40, 4-1BB and ICOS in 29 patients with RGH and 29 normal human controls. Results The proportions of NKG2D-positive and NKp46-positive NK cells significantly decreased in patients with RGH than those in the normal human controls [(93.3 ± 5.4)% vs (96.9 ± 2.5)%, (88.9 ± 8.7)% vs(93.4 ± 4.1)%, respectively, both P < 0.01]. Between the patients and controls, no significant difference was observed in the expression of NK cell inhibitory receptors, NKG2A [(41.8 ± 14.4)% vs (46.0 ± 14.7)%, P > 0.05] or KIR [(68.3 ± 19.1)% vs (69.1 ± 17.6)%, P > 0.05]. A lower expression of costimulatory molecule OX40 was noted in NK cells from patients with RGH compared with those in normal controls [(1.0 ± 1.1)% vs (1.8 ± 1.7)%, P < 0.05]. Conclusions Herpes simplex virus infection could down-regulate the expression of NK cell activating receptors and costimulatory molecules, subsequently suppress the activation of NK cells, and lead to the escape of virus-infected cells from the killing of NK cells.

Changes of T lymphocyte subsets and expression of costimulatory molecule CD154 on T-cells in peripheral blood from patients with ankylosing spondylitis / 中华风湿病学杂志

Objective To study T lymphocyte subsets and expression of costimulatory molecule CD154 on T-cells in peripheral blood from patients with ankylosing spondylitis and their changes after treated with Enbrel. Methods Sixty-six patients with AS(39 active and 27 inactive, 35 axial and peripheral joint involvement and 31 axial involvement only), 30 patients with rheumatoid arthritis(RA), 30 healthy volunteers were analyzed. The expression of CD154 on CD3+ T cell as well as T-cells subsets were evaluated using flow cytometry respectively. The changes of the expression of costimulatory molecule CD154 in 39 active AS patients(Enbrel treatment or placebo treatment) were observed in a randomized, double-blind, placebothan that of healthy volunteers, and CD154 expression on CD3+ T cells in peripheral blood in AS patients was on CD3+ T cells in the peripheral blood of active AS or AS patients with peripheral joint involvement were significantly higher than those in inactive or axial involvement only AS patients(P＜0.05), and CD154 on CD3+ placebo, in AS patients group, there was significant reduction in CD154 expression on CD3+ T cells in Enbrel group at week 6(P＜0.05), there was no significant difference between Enbrel group and healthy volunteers at week 6(P＞0.05). Conclusion T lymphocyte subsets are significantly abnormal and CD154 is overexpressed on T-cells in peripheral blood of patients with AS. A six-week course of treatment with Enbrel in active AS can induce a down-regulation of the expression of CD154 on T cells.

Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

Costimulatory and antigen-presenting molecules are essential to the initiation of T cell immunity to mycobacteria. The present study analyzed by immunocytochemistry, using monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase method, the frequency of costimulatory (CD86, CD40, CD40L, CD28, and CD152) and antigen-presenting (MHC class II and CD1) molecules expression on human lung cells recovered by sputum induction from tuberculosis (TB) patients (N = 22) and non-TB controls (N = 17). TB cases showed a statistically significant lower percentage of HLA-DR+ cells than control subjects (21.9 ± 4.2 vs 50.0 ± 7.2 percent, P < 0.001), even though similar proportions of TB cases (18/22) and control subjects (16/17, P = 0.36) had HLA-DR-positive-stained cells. In addition, fewer TB cases (10/22) compared to control subjects (16/17) possessed CD86-expressing cells (P = 0.04; OR: 0.05; 95 percentCI = 0.00-0.51), and TB cases expressed a lower percentage of CD86+ cells (P = 0.04). Moreover, TB patients with clinically limited disease (£1 lobe) on chest X-ray exhibited a lower percentage of CD86-bearing cells compared to patients with more extensive lung disease (>1 lobe) (P = 0.02). The lower expression by lung cells from TB patients of HLA-DR and CD86, molecules involved in antigen presentation and activation of T cells, may minimize T cell recognition of Mycobacterium tuberculosis, fostering an immune dysfunctional state and active TB.

An increased expression of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease / 国际眼科杂志(Guoji Yanke Zazhi)

· AIM: To investigate the expression and the possible implication of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease.· METHODS: Sampling was done from erythema nodosum of 5 patients with Beh(c)et's disease and normal skin of 2 healthy individuals. Immunohistochemical staining was performed to examine the expression of CD4, CD8, CD19, CD68, HLA-DR,CD40 and CD40L molecules in the obtained tissues.· RESULTS: Approximately 90% of epidermic cells in erythema nodosum expressed CD40 molecule. In the dermis and subcutaneous tissue, a significantly increased number of CD4+Tcells, CD8+Tcells, CD19+cells, CD68+cells, HLA-DR+cells,CD40L+cells, and CD40+cells were observed in the erythema nodosum as compared with that in normal skin. Double staining showed that CD40L molecules were expressed on 45% of CD4+T cells. CD40 molecules were expressed on 100% CD68+ cells and 59.2% of HLA-DR+cells respectively.· CONCLUSION: A number of CD40/CD40L costimulatory molecules are upreguiated in the erythema nodosum of patients with Behcet's disease.

Changes of Signal Transduction of Toll-Like Receptors in Children with Acute Idiopathic Thrombocytopenic Purpura / 实用儿科临床杂志

Objective To investigate the role of signal transduction of toll-like receptors(TLRs)in immunological pathogenesis in children with acute idiopathic thrombocytopenic purpura(ITP).Methods Thirty children with actue ITP and 30 age-matched healthy children were studied.Real-time fluorescent quantitative PCR was used to evaluate the levels of TLR 1-10 and signal transducing molecules,and cytokines associated with TLRs,such as IL-1?,granulocyte-macrophage colony-stimulating factor(GM-CSF),macrophage colony-stimulating factor(M-CSF)and IFN-?/? mRNA.Expressions of co-stimulatory molecules such as CD40,CD80 and CD86 in mo-nocyte/macrophage(MC)was analyzed by flow cytometry.Results Compared with healthy control group,the mRNA levels of TLR3,7,8 and 9 in ITP group were significantly up-regulated(Pa0.05).Transcription le-vels of MyD88-dependent and-independent pathway molecules such as MD-2,MyD88,IRAK-4,TRAF6,TAK1,TRIF,TRAM,TBK-1 and IFN-? were significantly up-regulated in acute ITP(Pa0.05).Conclusion Aberrant activation of toll-like receptors signaling may be one of the initiating factors of immune dysfunction in children with acute ITP.

Costimulatory molecules and allograft rejection / 肿瘤研究与临床

Allograft rejection after xero organ transplantation rejection, especially acute rejection is still the major reason of failure and death. Active T cell play key roles in allograft rejection. It has been showed that the expressions of costimulatory molecules are associated with xero organ transplantation rejection. The pathways of CD28/CTLA-4 and CD40/CD40L are important costimulatory pathways that cause T cell activation.The article emphasizes on the role of CD28/CTLA-4-B7 pathway in allograft rejection.

Effects of rhG-CSF mobilization on immunological characteristics of peripheral blood grafts and steady-state bone marrow / 中国实用内科杂志

Objective To explore the difference of immunological characteristics between recombination human granulocyte colony-stimulating factor(rhG-CSF)mobilized peripheral blood grafts(G-PB)and steady-state bone marrow grafts(SS-BM).Methods From April to October 2003,G-PB and SS-BM of 15 related donors were collected.T cell subgroups,dendritic cells(DC),monocytes and the expression of CD28 costimulatory molecules on T cells were determined by multicolor flow cytometry.The lymphocyte proliferation ability and the quantities of interleukin-4(IL-4)and interferon-?(IFN-?)secreted by T cells were determined using MTT assays and sandwich ELISA.Results The absolute numbers of monocytes,CD3+,CD4+ and CD8+ T cells,and the ratios of CD4/CD8 in G-PB were significantly higher than those in SS-BM,respectively(P0.05).The quantities of IFN-? and IL-4 secreted by T cells per micromilter in G-PB was significantly higher than those in SS-BM(P0.05).The absolute numbers of DC1 and DC2 in G-PB were significantly higher than those in SS-BM(P0.05).Conclusion It is concluded that the difference of immunological characteristics between G-PB and SS-BM may explain the lower incidence of GVHD and lower relapse rate after SS-BM and G-PB transplantation.

Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

BACKGROUND: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. METHODS: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. RESULTS: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. CONCLUSION: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

Abnormal expression of costimulatory molecules CD_(28)and CD_(137)on PBMC from patients with chronic nephritis / 中国实用内科杂志

Objectives To investigate the expression features and roles of the costimulatory molecules and T lymphocyte subsets from patients with chronic nephritis.Methods The expression of the costimulatory molecules CD 28 and CD 137 on PBMC (peripheral blood mononuclear cells) and T lymphocyte subsets from 52 patients with chronic nephritis were studied by immunophenotyping and flow cytometry analysis.Results The T lymphocyte subsets from patients with chronic nephritis showed an obvious imbalance with reversing CD 4/CD 8 ratio,decreasing CD + 4T cells and increasing CD + 8T cells.The expression of the costimulatory molecule CD 28 on T cells was significantly lower compared with normal controls (P

Expression of CD28-B7 costimulatory molecules on peripheral blood cells in myasthenia gravis / 中国免疫学杂志

Objective:To investigate the relationship between the pathogeny and expression of CD28 B7 costimulatory molecules on peripheral blood cells in myasthenia gravis.Methods:Expression of CD28?CTLA4 and their ligants B7 1?B7 2 on CD4 + and CD8 + T lymphocytes in 18 patients with MG and 16 healthy controls were examined by flow cytometry.Results:In MG group,the expression of CD28?CTLA4?B7 1?B7 2 molecules were increased.The increased CD28 + cells were mainly of CD4 +T lymphocytes subset.The increased CTLA4 + cells were mainly of CD8 + T lymphocyte subset;There was no significant difference in the expressions of B7.1 and B7.2 molecules on CD4 + or CD8 + T lymphocytes between two groups.Conclusion:The pathogeny of myasthenia gravia is associated with the increased expression of CD28 B7 costimulatory molecules.Examining of CD28 B7 costimulatory molecules on peripheral blood cells may reflect the immune state of MG patients,and is helpful to the diagnosis and treatment.