Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansi...Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.展开更多
基金grant FIS PI#13/00029(Fondo de Investigaciones Sanitarias,Ministry of Health,Spanish Government and cofunded by the European Union ERDF/ESF,“Investing in your future”)LE093U13 and Unit of Excellence Research UIC#012(Department of Education of the Regional Government,Junta de Castilla y Leon)+3 种基金Gerencia Regional de Salud(BIO/01/15)which were awarded to J.I.R.B.Miguel Servet National Grant(Health National Organization Research)CP12/03063,CPII17/00002 and FIS PI16/00002(Instituto de Salud Carlos III and cofunded by European Union ERDF/ESF,“Investing in your future”)Gerencia Regional de Salud GRS963/A/2014,GRS1142/A/2015 and GRS1505/A/2017 funded the research of M.L.R.G.The National Network CIBERONC(Oncology Research Program,referenced as CB16/12/00480)also cofunded this work.P.S.is funded by grant 31003A-176356 of the Swiss National Science Foundation.A.W.is funded by the grants Deutsche Krebshilfe(70112451)Deutsche Forschungsgemeinschaft(SFB1039,and FOR2438).
文摘Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.
