A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis / 中国当代儿科杂志

OBJECTIVES@#To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA.@*METHODS@#In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14+ mononuclear cells, CD4+ T lymphocytes, and CD8+ T lymphocytes.@*RESULTS@#The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4+ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8+ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14+ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05).@*CONCLUSIONS@#The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.

Correlation and clinical significance of VISTA expression and cervical squamous cell carcinoma / 中华肿瘤杂志

Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.

Knockout of BRCC3 aggravates acute GVHD in allogeneic hematopoietic stem cell transplant recipient mice / 中华放射医学与防护杂志

Objective:To investigate the effect and underlying mechanism of BRCC3 knockout on acute GVHD(aGVHD) of mice.Methods:A total of 12 recipient C57BL/6J mice were divided into two groups, including 6 wild type(WT) and BRCC3 -/-(KO). The recipients were exposed to 4.5 Gy + 4.5 Gy 60Co γ-rays in total body irradiation (TBI) at 30 min intervals. At 6 h post-irradiation, 1×10 7bone marrow cells and 8×10 6 splenocytes from BALB/c mice were infused into C57BL/6J mouse via tail vein to develop aGVHD mouse model. BRCC3 was specifically knocked out in aGVHD mouse model. The organ damage was examined through histopathology. The levels of serum cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cytometric bead array (CBA), respectively. Spleen, liver and small intestine lymphocytes were isolated at 9 d post-transplantation, and the infiltration and activation of T cells in the target organs were assayed using flow cytometry. Results:The absence of BRCC3 in recipient mice significantly shortened survival ( P<0.05) with increased liver injury of aGVHD mice. In BRCC3 -/-recipient mice, the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly higher than those in the spleen( t=6.53, 5.52, P<0.05), and the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly increased in the liver ( t=3.74, 3.19, P<0.05). Similarly, the proportions of CD8+ T cells, CD8+ CD25+ T cells and CD8+ CD69+ T cells were significantly elevated in the small intestine ( t=3.52, 4.06, 3.29, P<0.05). Conclusions:BRCC3 deletion increased the proliferation and activation of donor CD8+ T cells and aggravated aGVHD, which might provide a new prevention and treatment target for aGVHD.

The clinical significance of the transforming growth factor-β receptor I expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the clinical significance of the transforming growth factor-β receptor I (TGF-βRⅠ) expression in na?ve CD4 + T cells from patients with systemic lupus erythematosus (SLE). Methods:Na?ve CD4 + T cells were purified using magnetic microbeads from peripheral blood mononuclear cells of SLE patients and healthy controls. Real-time quantitative PCR was used to detect TGF-βRⅠ mRNA level, and flow cytometry was used to detect the percentage of CD69 +CD4 + T cells. Data were analyzed by t test and Pearson correlation analysis. Results:The level of TGF-βR Ⅰ mRNA in na?ve CD4 + T cells from SLE patients was significantly lower than that in healthy controls [(0.674±0.873) vs (1.445±1.112), t=2.301, P<0.05]. The TGF-βR Ⅰ mRNA level was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) ( r=-0.376, P<0.05), erythrocyte sedimentation rate (ESR) ( r=-0.376, P<0.05), serum creatinine ( r=-0.323, P<0.05) and 24 h urine protein ( r=-0.331, P<0.05), and positively correlated with serum com-plement C3 ( r=0.528, P<0.01). The level of TGF-βRⅠ mRNA level in na?ve CD4 + T cells in SLE patients with renal involvement was lower than that in SLE patients without renal involvement [(0.525±0.536) vs (1.071±1.007), t=2.198, P<0.05]. The TGF-βR Ⅰ mRNA level in the na?ve CD4 + T cells in anti-dsDNA antibody positive group was lower than that in the anti-dsDNA antibody negative group [(0.344±0.315) vs (0.958±1.076), t=2.277, P<0.05]. The expression of TGF-βRⅠ mRNA in na?ve CD4 + T cells from SLE patients was reduced after 24 h stimulation with anti-CD3/CD28 beads [(0.047±0.013) vs (1.008±0.129), t=14.38, P<0.01], which was partially reversed by dexamethasone treatment [(0.240±0.042) vs (0.047±0.013), t=7.845, P<0.01]. Meanwhile, dexamethasone significantly decreased the expression of CD69 in CD4 + T cells [(15.0±2.1)% vs(34.9±2.0)%, t=32.57, P<0.01]. Conclusion:The abnormally low expression of TGF-βRⅠ in na?ve CD4 + T cells may be involved in the pathogenesis of SLE. Glucocorticoid treatment can upregulate the expression of TGF-βRI and inhibit the activation of T cells, This suggests suggesting that TGF-βRⅠ may be a potential target for SLE treatment.

Single-cell Analysis of CAR-T Cell Activation Reveals A Mixed T1/T2 Response Independent of Differentiation / 基因组蛋白质组与生物信息学报·英文版

The activation mechanism of chimeric antigen receptor (CAR)-engineered T cells may differ substantially from T cells carrying native T cell receptor, but this difference remains poorly understood. We present the first comprehensive portrait of single-cell level transcriptional and cytokine signatures of anti-CD19/4-1BB/CD28/CD3ζ CAR-T cells upon antigen-specific stimulation. Both CD4 helper T (T) cells and CD8 cytotoxic CAR-T cells are equally effective in directly killing target tumor cells and their cytotoxic activity is associated with the elevation of a range of T1 and T2 signature cytokines, e.g., interferon γ, tumor necrotic factor α, interleukin 5 (IL5), and IL13, as confirmed by the expression of master transcription factor genes TBX21 and GATA3. However, rather than conforming to stringent T1 or T2 subtypes, single-cell analysis reveals that the predominant response is a highly mixed T1/T2 function in the same cell. The regulatory T cell activity, although observed in a small fraction of activated cells, emerges from this hybrid T1/T2 population. Granulocyte-macrophage colony stimulating factor (GM-CSF) is produced from the majority of cells regardless of the polarization states, further contrasting CAR-T to classic T cells. Surprisingly, the cytokine response is minimally associated with differentiation status, although all major differentiation subsets such as naïve, central memory, effector memory, and effector are detected. All these suggest that the activation of CAR-engineered T cells is a canonical process that leads to a highly mixed response combining both type 1 and type 2 cytokines together with GM-CSF, supporting the notion that polyfunctional CAR-T cells correlate with objective response of patients in clinical trials. This work provides new insights into the mechanism of CAR activation and implies the necessity for cellular function assays to characterize the quality of CAR-T infusion products and monitor therapeutic responses in patients.

Expression profile analysis of long noncoding RNAs and mRNAs in the human colon cancer cells regulated by VTCN1 / 上海交通大学学报（医学版）

Objective • To investigate the effect of V-set domain containing T cell activation inhibitor 1 (VTCN1) on long noncoding RNAs (lncRNAs) and mRNAs expression in colon cancer cells. Methods • VTCN1 was overexpressed by lentivirus plasmid in colon cancer cell line SW1116. RNA was extracted and sequenced. The differentially expressed lncRNAs and mRNAs were compared with the negative control group. The accuracy of RNA sequencing was verified by real-time quantitative PCR (qRT-PCR) using three differentially expressed lncRNAs and two mRNAs. BLAST2GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze and predict the functions of these differentially expressed lncRNAs and mRNAs. The online platform GEPIA18 (Gene Expression Profiling Interactive Analysis) was used to analyze the correlation between differentially expressed lncRNAs and survival of patients with colorectal cancer. Results • A total of 167 differential genes, i.e., 39 lncRNAs and 128 mRNAs, were identified by RNA sequencing in VTCN1 overexpressed SW1116 cells. The results of qRT-PCR were consistent with those of RNA sequencing. Bioinformatics analysis showed that these different genes regulated by VTCN1 may be involved in endoplasmic reticulum protein processing and RNA monitoring signaling pathways. In addition, three lncRNAs (DNA JC9-AS1, HCG27, and RP11-339B21.13), which were significantly up-regulated in colorectal cancer cells overexpressing VTCN1, were also independent predictors of overall survival of colorectal cancer patients. Conclusion • In colon cancer cells, VTCN1 regulates several downstream lncRNAs and mRNAs, which may be involved in endoplasmic reticulum protein processing and mRNA monitoring signaling pathways.

Piperacillin-Tazobactam-Induced Linear IgA Bullous Dermatosis Supported by a T-Cell Activation Assay

Linear immunoglobulin (Ig) A bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear IgA deposits at the basement membrane zone visualized with direct immunofluorescence (DIF). Most cases of LABD are idiopathic, but some are drug-induced with vancomycin being the most common causative agent. We herein report a patient presenting with blisters and erosive lesions, primarily in the intertriginous and flexor areas, consistent with a diagnosis of piperacillin-tazobactam-induced LABD based on the patient's clinical course and histopathology, DIF, and in vitro T-cell activation assay (TAA) findings. Only one case of piperacillin-tazobactam-induced LABD has been previously reported. In addition to its rarity, our case was also unique in that the skin lesions occurred in the intertriginous and flexor areas, uncommon locations for typical adult patients with LABD, and TAA strongly suggested an association with the causative drug.

Deubiquitinases as pivotal regulators of T cell functions / 医学前沿

T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs). DUBs are isopeptidases that cleave polyubiquitin chains and remove ubiquitin from target proteins, thereby controlling the magnitude and duration of ubiquitin signaling. It is now well recognized that DUBs are crucial regulators of T cell responses and serve as potential therapeutic targets for manipulating immune responses in the treatment of immunological disorders and cancer. This review will discuss the recent progresses regarding the functions of DUBs in T cells.

Activation of CD8+T cells regulated by γ-aminobutyric acid and its receptors / 器官移植

Objective To evaluate the effect of γ-aminobutyric acid (GABA) and its receptors upon the proliferation of CD8+T cells.Methods The splenic CD8+T cells of Balb/c mice were obtained by CD8+f cell magnetic bead sorting kit.Under the effect of CD3/CD28-activated magnetic bead,CD8+T cells were stimulated by different concentrations of GABA.5-bromo-2-deoxyuridine (BrdU) labeling and flow cytometry were performed to detect the proliferation of CD8+T cells.The expression levels of GABA-A and GABA-B receptor before and after CD8+T cell activation were compared by fluorescent quantitative real-time polymerase chain reaction (PCR).Result Flow cytometry result revealed that GABA could inhibit the proliferation of activated CD8+T cells,manifested as significant decrease in the quantity of CD152+CD8+T cells.Fluorescent quantitative real-time PCR demonstrated that GABA-A receptor subtypes α2,α6 and GABA-B receptor subtype 1a were expressed only when the CD8+T cells were activated.After CD8+T cell activation,the quantity of GABA-A receptor subtypes α3,αs,β2,β3,γ1,γ2 and θ were significantly increased,whereas the quantity of GABA-B2R and GABA-B1b did not significantly differ before and after CD8+T cell activation.Conclusions GABA can suppress the proliferation of activated CD8+T cells.The activation of CD8+T cells is regulated by GABA receptors.However,the underlying mechanism remains to be elucidated.

Vitamin C is taken up by human T cells via sodium-dependent vitamin C transporter 2 (SVCT2) and exerts inhibitory effects on the activation of these cells in vitro / 대한해부학회지

Vitamin C is an essential micronutrient that affects immune responses. T cells are one of the main players in acquired immunity and have been reported to be influenced by in vivo vitamin C supplementation. Yet, the way by which T cells uptake vitamin C and what direct effects vitamin C exerts on the cells are not known. To elucidate, we isolated human peripheral blood T cells and analyzed the expression of sodium-dependent vitamin C transporters (SVCT). T cells were activated in vitro in the absence or presence of vitamin C, before or after activation. As results, human T cells expressed SVCT2, but not SVCT1, and the expression level increased following activation. Vitamin C added in the culture media generally did not affect T-cell behaviors following activation, such as proliferation, apoptosis, expression of CD25 and CD69, and interleukin 2 secretion, regardless whether it was added before or after activation. However, exceptionally, high concentration vitamin C, when it was added before activation, but not after activation, did exert toxic effects on cell activation with respect to the above-mentioned parameters. In conclusion, we showed the expression of SVCT2 in human T cells for the first time. Vitamin C exerted toxic effects, at least in vitro, when the concentration was high and when it was given before activation. These toxic effects are not thought to be via anti-oxidant effects of vitamin C.

T cell receptor signaling pathway is overexpressed in CD4 + T cells from HAM/TSP individuals

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4+ T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3?), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70 kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3?, LCK, ZAP70, and VAV1 gene expression were increased in CD4+ T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3?, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3?, LCK, and VAV1 gene expression in CD4+ T cells, and these genes function on a synchronized way on the CD4+ T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.

Natural Treatment Alternative for Psoriasis: A Review on Herbal Resources.

Psoriasis is an immune mediated inflammatory disease, which is having no permanent cure. Though, there are several treatment methods to treat psoriasis, no particular medication claims a satisfactory and complete remedy. A wide range of synthetic therapeutic agents have also been reported to cause psoriasis as their adverse effect. Herbal drugs by virtue of their safe nature and easy availability may lend themselves as potential anti-psoriatic moieties. Before developing a herbal drug candidate the key players of psoriasis to develop should be thoroughly understood, which includes T-cell activation, T-cell trafficking, Cytokinase inhibition. The paper aims to explore the proliferation and activation mechanism of psoriasis, psoriasis caused by certain drugs and different plant resources known to have anti-psoriatic potential. A more scientific investigation on these herbal resources must be performed to develop a potent, safe and reliable therapy.

Early T cell activation gene-3 expression following isogenic half liver transplantation in mice / 中华普通外科杂志

Objective To explore the effect of different cold ischemia (CI)times on the patterns of intra-graft T cell activation gene-3 (TCA-3) expression early after isogeneic half liver transplantation (PLT)in mice. Methods The models of C57BL/6 full-size(FS) and PLT were established.The CI time was 1,4 and 8 h.Specimen were collected at 4 and 24 h post-reperfusion.Ribonuclease protection assays (RPA)was used to evaluate serial mRNA expression of the TCA-3 chemokine in all mice.Histopathology was used to examine cold ischemia injury in the liver grafts. Results A total of 45 control and 30 PLTs were performed.The survival rate at 7 day after control and PLT was 100％.Quantitative analysis demonstrated the levels of TCA-3 mRNA expression were low at 4 h after reperfusion in control group with 1,4,8 h CI.The levels of TCA-3 significandy increased at 4 h after reperfusion in PLT group with CI of 1,4,8 h and the difference between the two groups was statistically significant ( F =7.41,P ＜ 0.05 ). TCA-3 mRNA expression significantly decreased at 24 h after reperfusion in two groups. But the difference was not statistically significant ( P ＞ 0.05 ). Histopathology showed severer cold ischemia injury in PLT grafts compared with control grafts. Conclusions The expression of TCA-3 significandy increased early after PLT and played an important role in cold ischemia injury.TCA-3 could be used as the early therapeutic target for reducing ischemia injury in PLT grafts.

Loss of CD127 & increased immunosenescence of T cell subsets in HIV infected individuals.

Background & objectives: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naïve T cell subsets in HIV-infected and uninfected individuals. Methods: We characterized T cell subsets based on expression of these markers, and compared their expression pattern in HIV infected subjects and uninfected controls. We further assessed therapy generated changes in these subsets and expression of CD127 and CD57 on them. Results: There was a generalized decrease in naïve CD4 and CD8 T cells in HIV infected subjects. These changes in T cell subset distribution were related to antigen load. CD127 expression was significantly reduced in T cells from HIV infected subject. In association to this, HIV infected subjects had higher percentage of T cell subsets expressing CD57. Increased CD57 and reduced CD127 expression correlated with plasma viraemia and CD8 T cell activation state. Incomplete restoration of T cell subset proportions was observed, despite suppression of viral replication and increase in CD4 T cell counts. Further, the improvement was more pronounced in CD127 expression. Interpretation & conclusions: HIV infected subjects have reduced T cell regenerative capacity along with increased senescence, highlighting decreased proliferation and effector activities.

Regulatory role of BTLA signal in the initiation and early phase of T cell activation / 中国免疫学杂志

Objective:To observe the expression of BTLA on T cells during activation and further analyze its inhibitory effects on T cell activation in different phases.Methods: T cells from PBMC were enriched by negative selection using magnetic beads.Expression of BTLA,CTLA-4 and PD-1 on freshly isolated human T cells and kinetics expression of BTLA,CILA-4 and PD-1 on CD3 mAb stimulated T cells were examined by flow cytometry.T cells were stimulated by anti-CD3 mAb combined with anti-CD28 mAb in the presence of anti-BTLA mAb 8H9,then T cell proliferation was tested by MTT assay in the different culture time.Immature DCs were generated from monocytes cultured in the medium containing GM-CSF and IL-4, and further driven to maturation by anti-CD40 mAb.Expression of HVEM on DCs was measured by flow cytometry.T cells were co-cultured with DCs in the presence of soluble 8H9 or anti-HVEM antibody to block HVEM-BTLA interaction,T cell proliferation was measured by MTT assay.Results:Freshly isolated T cells exhibited high levels of BTLA expression, but not CTLA-4 and PD-1.After T cell activation, BTLA expression decreased on first 2 days, with rapidly increasing to high levels.Unlike BTLA, expression of CTLA-4 and PD-1 was gradually increased during T cell activation.8H9 significantly inhibited the proliferation of T cell stimulated by CD3 mAb and CD28 mAb.8H9 could still exhibit inhibitory effect on T cell proliferation after 24 h or 48 h of preactivation by CD3 mAb plus CD28 mAb stimulation.HVEM was highly expressed on immature DCs, and down-regulated on mature DCs.Blockade of BTLA by soluble 8H9 or anti-HVEM antibody enhanced DC-mediated T cell proliferation within 48 h.Conclusion: BTLA signal enhances the threshold of T cell activation and plays importantly negative regulatory role in the initiation and early phase of T cell activation.

Investigation of the Effective Dose of Agonistic 4-1BB Monoclonal Antibody in a Murine Colon Cancer Metastasis Model

PURPOSE: The aim of this study was to find the dose of agonistic 4-1BB monoclonal antibody (mAb) that results in optimal T cell activation. METHODS: Cancer was induced in mice by an intrahepatic parenchymal injection of 1x10(5) cells of CT26 cells. Cancer-carrying mice (n=84) were divided into seven groups and treated with either rat IgG or agonistic 4-1BB monoclonal antibody (mAb) (5microgram, 10microgram, 20microgram, 100microgram, 200microgram, or 300microgram). All treatments were administered intraperitoneally on days 7, 9, and 11. Mice from each group were sacrificed on days 14, 28, and 42. Harvested livers were weighed and the numbers of T cells in the splenocytes were analyzed with a FACS Vantage flow cytometer. RESULTS: Liver weights increased when 5microgram of agonistic 4-1BB mAb was administered, but showed no additional weight increase for doses greater than 10microgram. The absolute numbers of CD4+ and CD8+ T cells increased in groups treated with low doses of agonistic 4-1BB mAb (5microgram, 10microgram, or 20microgram), but did not increase in the groups treated with high doses of mAb (100microgram, 200microgram, or 300microgram). The levels of CD4/annexin V and CD8/annexin V increased as the dose increased, and the absolute cell numbers of CD4/annexin V were greater than those of CD8/annexin V. CONCLUSION: Liver weight, including the cancer mass, failed to increase at agonistic 4-1BB mAb doses greater than 10microgram. A high dose (> or =100microgram) of agonistic 4-1BB mAb resulted in lower counts of absolute T cells. This study suggests that a low dose (20microgram) of agonistic 4-1BB mAb can be used for optimal T cell activation in combination with other anti-cancer treatments.

Adhesion blocking experiment of vascular endotelial cells with platelets / 中国基层医药

Objective To discuss adhesion blocking experiment of vascular endotelial cells with platelets.Methods The expression,regulation and adhesion of CD226 on vascular endothelial cells incubated by sera from 10 PIH patients and 10 normal pregnant women repectively was detected by flow cytometry,then incubated with interacted platelets by PTA1/Ig protein.Results The positive rate of CD226 in PIH group was significantly higher than that in normal pregnant woman group(P

T cell response to cyclic citrullinated peptide in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To examine the role of synthetic cyclic citrullinated peptide (CCP) in T cell autoreactivity in rheumatoid arthritis (RA) by detecting T cell proliferation. Methods Twenty-nine RA, 8 primary Sjo gren syndrome (pSS) and 16 osteoarthritis (OA) patients were included in this study. Proliferation of T cells was measured by methyltetiazolium incorporation following incubation with CCP. Results T cell response to CCP was more common in RA patients than in controls. The response rate to CCP was higher in late RA than in early RA. However, the response wasn′t associated with disease activity. A strong association between T cell proliferation and RF, anti-CCP antibody was observed. Conclusions T cell proliferation in response to CCP was found in the majority of RA patients, even in early RA, suggesting that the citrullinated peptide play an important role in the pathogenesis of RA.

T Cell Activation in Ischemic Heart Disease

BACKGROUND: It was recently shown that human atherosclerotic plaque contains large numbers of T lymphocytes : this indicates that immune and inflammatory mechanism may be important factors in the pathogenesis of atherosclerosis. By measuring the soluble interleukin 2 receptor(sIL-2R) level we can evaluate the activation of T lymphocyte. The purpose of this study is to evaluate relationship between T cell activation and ischemic heart disease by measuring the soluble interleukin 2 receptor (sIL-2R) level in patient with ischemic heart disease. METHOD: Seventy-two patients(40 males and 32 female, mean age : 56.5+/-9.9 years) who were taken coronary angiography were included in this study. Among them, 49 patients showed abnormal coronary angiographic findings and 23 patients showed normal coronary angiographic findings. Ten mililiters of arterial blood was drawn at the time of coronary angiography. The blood was allowed to coagulate and then the serum was removed and tested in duplicate for soluble interleukin 2 receptor (sIL-2R) level by ELISA. RESULTS: 1) The soluble interleukin 2 receptor (sIL-2R) level was significantly different between abnormal coronary angiographic findings and normal coronary angiographic findings (P 0.05), but showed increasing tendency with clinical severity. 3) According to numbers of involved coronary vessels, soluble interleukin 2 receptor (sIL-2R) level was not significantly different between single vessel disease group and multivessels disease groups (p > 0.05). CONCLUSION: T lymphocyte activation, as reflected in elevated soluble interlekin 2 receptor (sIL-2R) level, is frequent in patient with ischemic heart disease. In the further we will investigate relationship between clinical diagnosis of ischemic heart disease of the numbers of involved coronary vessels and T cell activation.

Characterization of the nover late T cell activation proteins, 519 and 520

The late T cell activation gene, 519, is expressed in antigen specific, growth factor dependent T cell lines and clones but not in T or B cell tumors, other hematopoietic cells, tonsil, muscle, lung, or liver. Resting peripheral blood lymphocytes (PBLs) express little or no 519mRNA, but levels increase dramatically 5~7 days after activation with alloantigen or mitogen. Four alternatively spliced transcripts of the gene exist. 520 cDNA, the predominate gene transcript, encodes a protein of 144 amino acids and has a potentially cleavable hydrophobic leader of 15 amino acids at the amino terminus. The 519 transcript encodes a 129 amino acid product. An polyclonal antiserum was produced by immunizing a rabbit with a synthetic peptide corresponding to the second hydrophobic region common to both 519 and 520. 14.3 and 15.5kD protein bands were immunoprecipitated (IP) from radiolabled in-vitro translated products, 519 and 520 respectively. A protein of 14.3kD was detected by IP of in-vivo 35S cysteine and methionine radiolabled cytotoxic T lymphocytes (CTL) cells. Western blotting of lysates from a CTI line and a B cell tumor line revealed a distinct band at 14.3kD only in CTL lanes. Both CTL and peripheral blood lymphocytes expressed the greatest amount of 519/520 protein in cells 5~7 days after stimulation. Western blotting of differential centrifugation samples localized 519/520 protein to the granule layer. Comparison of 519/520 proteins with other known protin sequences identified homology with surfactant associated and sphyngolipid activating proteins. A homologous gene(NKC5) is present in natural killer cells (NK). The increase in the amount of the 519/520 protein product in CTL and PBL parallel increases in mRNA expression. 519/520 and related gene products are present in CTL, PBL and NK cells, have structural similarity with lipid associating proteins.