The B7-family inducible costimulator(ICOS)activates phosphoinositide-3 kinase(PI3K)and augments calcium mobilization triggered by the T-cell receptor(TCR).We surprisingly found that the entire cytoplasmic domain of IC...The B7-family inducible costimulator(ICOS)activates phosphoinositide-3 kinase(PI3K)and augments calcium mobilization triggered by the T-cell receptor(TCR).We surprisingly found that the entire cytoplasmic domain of ICOS is dispensable for its costimulation of calcium mobilization.This costimulatory function relies on the unique transmembrane domain(TMD)of ICOS,which promotes association with the tyrosine kinase Lck.TMD-enabled Lck association is also required for p85 recruitment to ICOS and subsequent PI3K activation,and Lck underlies both the bystander and costimulatory signaling activity of ICOS.TMD-replaced ICOS,even with an intact cytoplasmic domain,fails to support T FH development or GC formation in vivo.When transplanted onto a chimeric antigen receptor(CAR),the ICOS TMD enhances interactions between T cells and antigen-presenting target cells.Therefore,by revealing an unexpected function of the ICOS TMD,our study offers a new perspective for the understanding and potential application of costimulation biology.展开更多
AIM: To explore the role and significance of costimulatory molecules B7H1,B7H2 and ICOS within tissues of human gastric carcinoma and the possible mechanisms in tumor escape.
METHODS: mRNA expressions of costimulatory...AIM: To explore the role and significance of costimulatory molecules B7H1,B7H2 and ICOS within tissues of human gastric carcinoma and the possible mechanisms in tumor escape.
METHODS: mRNA expressions of costimulatory molecules including B7H1,B7H2,ICOS and B7-1 in tissues of human gastric carcinoma were investigated by in situ hybridization using digoxigenin-labeled oligonucleotide-probes. The tissue of chronic gastric ulcer was used as a control. All data were analyzed by SPSS statistic software.
RESULTS: At the site of gastric carcinoma, mRNA expression levels of B7H1, B7H2 and ICOS were much higher than that of B7-1. Their mRNA positive expression indexes were 0.512±0.333, 0.812±0.454, 0.702±0.359 and 0.293±0.253, respectively. The positively stained cells were mainly tumor infiltrating lymphocytes (TILs), and some tumor cells. The difference between them was greatly significant P＜0.005. The mRNA expression levels of four molecules were not correlated to the pathological grade and matastasis of gastric carcinoma.
CONCLUSION: ICOS-B7H costimulatory pathway may be predominant at the site of gastric carcinoma. B7-1mRNA might be the basis of ICOS-B7H interaction. ICOS-B7H interaction induces the production of IL-10 which inhibits the antitumor immune responses. Therefore, it is supposed that ICOS-B7H costimulatory pathway may be involved in the negative regulation of cell-mediated immune responses.展开更多
A new off-axis integrated cavity output spectroscopy （ICOS） is coupled to Weiss equilibrator for continuous high- resolution dissolved methane measurement in the surface ocean. The time constant for the equilibrator...A new off-axis integrated cavity output spectroscopy （ICOS） is coupled to Weiss equilibrator for continuous high- resolution dissolved methane measurement in the surface ocean. The time constant for the equilibrator in freshwater at room temperature is determined via dis-equilibration and re-equilibration experiments. The constant for methane is about 40 min. The system is calibrated using a standard gas of 3.980×10-6, and the precision of the ICOS for methane is 0.07%. This system is equipped onboard to measure the spatial distribution in methane concentrations of South Yellow Sea （SYS） along the cruise track from Shanghai to Qingdao. Result shows that the methane concentration varies from 2.79 to 36.36 nmol/L, reveals a significant pattern of methane source in SYS, and a distinct decreasing trend from south to north. The peak value occurs at the coast area outside mouth of the Changjiang River, likely to be affected by the Changjiang diluted water mass dissolving a large amount of rich in methane. Moreover, all the surface waters are oversaturated, air-to-sea fluxes range from 98.59 to 5 485.35 μmol/（m2·d） （average value （1 169.74±1 398.46） μmol/（m2·d））, indicating a source region for methane to the atmosphere. Key words： methane, equilibrator, off-axis integrated cavity output spectroscopy （ICOS）, South Yellow Sea展开更多
基金This work wasfunded in part by the Ministry of Science and Technology“973"program(Grant No.2014CB542501)the National Natural Science Foundation of China(Grant Nos.81330070,81425011,81621002,and 81761128019)+2 种基金the Tsinghua-Peking Centerfor Life SciencesThis work was also funded in part by the Bill&Melinda Gates Foundationthe Howard Hughes Medical lnstitute.
文摘The B7-family inducible costimulator(ICOS)activates phosphoinositide-3 kinase(PI3K)and augments calcium mobilization triggered by the T-cell receptor(TCR).We surprisingly found that the entire cytoplasmic domain of ICOS is dispensable for its costimulation of calcium mobilization.This costimulatory function relies on the unique transmembrane domain(TMD)of ICOS,which promotes association with the tyrosine kinase Lck.TMD-enabled Lck association is also required for p85 recruitment to ICOS and subsequent PI3K activation,and Lck underlies both the bystander and costimulatory signaling activity of ICOS.TMD-replaced ICOS,even with an intact cytoplasmic domain,fails to support T FH development or GC formation in vivo.When transplanted onto a chimeric antigen receptor(CAR),the ICOS TMD enhances interactions between T cells and antigen-presenting target cells.Therefore,by revealing an unexpected function of the ICOS TMD,our study offers a new perspective for the understanding and potential application of costimulation biology.
文摘AIM: To explore the role and significance of costimulatory molecules B7H1,B7H2 and ICOS within tissues of human gastric carcinoma and the possible mechanisms in tumor escape.
METHODS: mRNA expressions of costimulatory molecules including B7H1,B7H2,ICOS and B7-1 in tissues of human gastric carcinoma were investigated by in situ hybridization using digoxigenin-labeled oligonucleotide-probes. The tissue of chronic gastric ulcer was used as a control. All data were analyzed by SPSS statistic software.
RESULTS: At the site of gastric carcinoma, mRNA expression levels of B7H1, B7H2 and ICOS were much higher than that of B7-1. Their mRNA positive expression indexes were 0.512±0.333, 0.812±0.454, 0.702±0.359 and 0.293±0.253, respectively. The positively stained cells were mainly tumor infiltrating lymphocytes (TILs), and some tumor cells. The difference between them was greatly significant P＜0.005. The mRNA expression levels of four molecules were not correlated to the pathological grade and matastasis of gastric carcinoma.
CONCLUSION: ICOS-B7H costimulatory pathway may be predominant at the site of gastric carcinoma. B7-1mRNA might be the basis of ICOS-B7H interaction. ICOS-B7H interaction induces the production of IL-10 which inhibits the antitumor immune responses. Therefore, it is supposed that ICOS-B7H costimulatory pathway may be involved in the negative regulation of cell-mediated immune responses.
基金The Scientific Research Foundation of Third Institute of Oceangraphy under contract No.2013004the National Natural Science Foundation of China(NSFC)under contract Nos 40906102 and 41230529the CHINARE under contract Nos 2012–2013(01–04–02),(01–02–01)and(03–04–02)
文摘A new off-axis integrated cavity output spectroscopy （ICOS） is coupled to Weiss equilibrator for continuous high- resolution dissolved methane measurement in the surface ocean. The time constant for the equilibrator in freshwater at room temperature is determined via dis-equilibration and re-equilibration experiments. The constant for methane is about 40 min. The system is calibrated using a standard gas of 3.980×10-6, and the precision of the ICOS for methane is 0.07%. This system is equipped onboard to measure the spatial distribution in methane concentrations of South Yellow Sea （SYS） along the cruise track from Shanghai to Qingdao. Result shows that the methane concentration varies from 2.79 to 36.36 nmol/L, reveals a significant pattern of methane source in SYS, and a distinct decreasing trend from south to north. The peak value occurs at the coast area outside mouth of the Changjiang River, likely to be affected by the Changjiang diluted water mass dissolving a large amount of rich in methane. Moreover, all the surface waters are oversaturated, air-to-sea fluxes range from 98.59 to 5 485.35 μmol/（m2·d） （average value （1 169.74±1 398.46） μmol/（m2·d））, indicating a source region for methane to the atmosphere. Key words： methane, equilibrator, off-axis integrated cavity output spectroscopy （ICOS）, South Yellow Sea
