title: Kinetics of the CTLA-4 isoforms expression after T-lymphocyte activation and role of the promoter polymorphisms on CTLA-4 gene transcription.
abstract: Cytotoxic T lymphocyte antigen 4 (CTLA-4) plays a key inhibitory role during T lymphocyte activation. The CTLA4 gene is translated into two proteic isoforms: a full-length protein (flCTLA-4) and a soluble counterpart. We explored the expression of both isoforms on healthy subjects. Whereas in non-stimulated cells the flCTLA-4 isoform is predominant, after stimulation the expression of the soluble form rapidly increases, reaching its maximum 24h after and falling again to the basal levels 72 h after stimulation. In contrast, the flCTLA-4 mRNA levels increase is slower, reaching the maximum level 72 h after stimulation. The presence of the T allele in the promoter positions -1722 and -318 is associated with an increased transcriptional activity and this effect seems to be synergic. We conclude that the kinetics of CTLA-4 isoform expression are sequential, and that the promoter polymorphisms -1722(C/T) and -318(C/T) are involved in the control of the CTLA4 transcription.
authors.affiliation: Hematology Department, Institut Català d'Oncologia, Hospital Josep Trueta, IDIBGi, Girona, Spain.
authors.forename: Arianne
authors.initials: A
authors.lastname: Pérez-García
authors.forename: Gemma
authors.initials: G
authors.lastname: Osca
authors.forename: Anna
authors.initials: A
authors.lastname: Bosch-Vizcaya
authors.forename: Nichollas
authors.initials: N
authors.lastname: Kelleher
authors.forename: Nazly Y
authors.initials: NY
authors.lastname: Santos
authors.forename: Rocío
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Yolanda
authors.initials: Y
authors.lastname: González
authors.forename: Josep M
authors.initials: JM
authors.lastname: Roncero
authors.forename: Rosa
authors.initials: R
authors.lastname: Coll
authors.forename: Maite
authors.initials: M
authors.lastname: Serrando
authors.forename: Natàlia
authors.initials: N
authors.lastname: Lloveras
authors.forename: Esperanza
authors.initials: E
authors.lastname: Tuset
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
mesh_terms: D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008213:Lymphocyte Activation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism*; D013030:Spain; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics
chemical_list: D060908:CTLA-4 Antigen; D020033:Protein Isoforms