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http://purl.uniprot.org/citations/24515893http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24515893http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24515893http://www.w3.org/2000/01/rdf-schema#comment"Mitogenic stimulation of lymphocytes involves alkalinization of intracellular pH (pHi ). Subsequent pHi regulation may involve HCO3 (-) extrusion through Cl(-) /HCO3 (-) exchangers and/or Na(+) -HCO3 (-) co-transporters with acid-loading capability. Abnormalities in these mechanisms could result in immune dysfunctions, as suggested by the CD8(+) T-cell expansion encountered in mice lacking Ae2 (a widely expressed acid loader with electroneutral and Na(+) -independent Cl(-) /HCO3 (-) anion-exchange activity). Here we report that CD8(+) T cells but not CD4(+) T cells or other lymphocyte populations, are crucially dependent on Ae2 for pHi regulation. While total lymphocytes (including isolated CD4(+) T cells) exhibit Ae1 expression and Na(+) -HCO3 (-) co-transport with acidifying potential, CD8(+) T cells lack these acid-loading mechanisms. In Ae2-KO mice, CD4(+) but not CD8(+) T cells upregulate these potential Ae2 surrogates. As a consequence, Ae2-KO CD8(+) T cells exhibit alkalinized pHi , and dramatically increase their pHi upon CD3 stimulation. Moreover, stimulated Ae2-deficient CD8(+) T cells show enhanced intracellular production of IL-2 and membrane expression of its receptor IL-2Rα, together with increased cell proliferation and activation. These findings demonstrate that CD8(+) T cells are critically dependent on Ae2 for pHi homeostasis and tuning of cell proliferation and activation. Ae2 thus constitutes a novel target to modulate CD8(+) T-cell responses."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.org/dc/terms/identifier"doi:10.1002/eji.201344218"xsd:string
http://purl.uniprot.org/citations/24515893http://purl.org/dc/terms/identifier"doi:10.1002/eji.201344218"xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Ferrer A."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Ferrer A."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Lopez M."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Lopez M."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Prieto J."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Prieto J."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Saez E."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Saez E."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Oude Elferink R.P."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Oude Elferink R.P."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Banales J.M."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Banales J.M."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Concepcion A.R."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Concepcion A.R."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Hervas-Stubbs S."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Hervas-Stubbs S."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Medina J.F."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Medina J.F."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Portu A."xsd:string
http://purl.uniprot.org/citations/24515893http://purl.uniprot.org/core/author"Portu A."xsd:string